Unknown primary tumors

An unknown primary tumor (UPT) is defined by the presence of a metastatic cancer without a known primary site of origin despite a standardized diagnostic workup. Clinically, UPTs show rapid progression and early dissemination, with signs and symptoms related to the metastatic site. The molecular bases of their biology remain largely unknown, with no evidence as to whether they represent a distinct biological entity. Immunohistochemistry remain the best diagnostic tool in term of cost-effectiveness, but the time-consuming "algorithmic process" it relies on has led to the application of new molecular techniques for the identification of the primary site of UPTs. For example, several microarra…

Regulatory cytokine gene polymorphisms and risk of colorectal carcinoma.

It is well established that cancer arises in chronically inflamed tissue, and this is particularly notable in the gastrointestinal tract. Classic examples include Helicobacter pylori-associated gastric cancer, hepatocellular carcinoma, and inflammatory bowel disease-associated colorectal cancer. Growing evidence suggests that these associations might be not casual findings. Focusing on individual cytokines has generated evidence that anti-inflammatory cytokine interleukin (IL)-10 and transforming growth factor-beta1 (TGF-beta1) may have a complex role in gastrointestinal carcinogenesis. As an example, IL-10-deficient mice develop severe atrophic gastritis and a chronic enterocolitis, develo…

“Randomised trial comparing biweekly oxaliplatin plus oral capecitabine versus oxaliplatin plus i.v. bolus fluorouracil/leucovorin in metastatic colorectal cancer patients: results of the Southern Italy Cooperative Oncology study 0401”.

PURPOSE: Oxaliplatin combined with either fluorouracil/leucovorin (OXAFAFU) or capecitabine (OXXEL) has a demonstrated activity in metastatic colorectal cancer patients. We aimed at comparing these two regimens in terms of response rate (RR), safety, progression-free survival (PFS), and quality of life (QoL) of patients. METHODS: A total of 322 patients with metastatic colorectal cancer were randomized to receive biweekly: oxaliplatin 100 mg/m(2) i.v. on day 1, capecitabine 1,000 mg/m(2) orally twice daily from day 1 to day 11 (OXXEL); or oxaliplatin 85 mg/m(2) i.v. on day 1; 6S-leucovorin 250 mg/m(2) i.v. and fluorouracil 850 mg/m(2) i.v. on day 2 (OXAFAFU). RESULTS: Eleven complete and 42…

Weekly docetaxel (wDOC) for the treatment of metastatic breast cancer (MBC): A literature based meta-analysis

Combination chemotherapy with mitomycin C, vindesine and melphalan for refractory metastatic breast cancer.

A combination of mitomycin C, vindesine and melphalan was administered to 33 patients with heavily pretreated refractory breast cancer. The overall response rate was 27% with a mean duration of more than 10.2 months. A stabilization with a mean duration of 5.1 months was seen in 56% of cases, while 20% of patients progressed. Gastrointestinal toxicity, mostly grade 1 or 2 nausea/vomiting was seen in 85% of cases, grade 1 or 2 leukopenia in 60% of patients, and grade 1 or 2 thrombocytopenia in 42%. Considering the good compliance of this regimen and the poor prognosis of patients with refractory advanced breast cancer, this combination can be useful as a palliative treatment of breast carcin…

Erythromycin reverses the daunomycin resistance of MEL-DRTL cells

“Impact of pathological response on survival in stage IIIB T4 LABC patients:long-term outcome of an Italian multicentric study”

“Evaluating the prognostic role of serum extracellular domain (ECD) of HER-2/neu (s-HER2) in patients (PTS) with metastatic (M) breast cancer (BC): results of an observational study”

"Weekly regimen of cisplatin (CDDP),epirubicin (EPI), fluorouracil (5FU) and folinic acid (FA) with G-CSF is active in advanced gastroesophageal (GE) and gastric (G) cancer: results of a phase II study”

L’anemia nel paziente oncologico

Long-term outcomes in stage IIIB breast cancer patients who achieved less than a pathological complete response (pCR) after primary chemotherapy.

Abstract Learning Objectives After completing this course, the reader will be able to: Summarize the main risk factors for relapse in patients with T4 breast cancer after neoadjuvant chemotherapy.Evaluate the role of hormone receptors and HER-2 as determinants of risk of relapse after neoadjuvant treatment.Compare the difference in outcomes between patients who achieve less than pCR in relation to receptor status. This article is available for continuing medical education credit at CME.TheOncologist.com. Purpose. Pathological complete response (pCR) to primary chemotherapy is the main determinant for improved disease-free survival (DFS) and overall survival (OS). The primary endpoints of ou…

Gemcitabine plus vinorelbine in stage IIIB or IV non-small cell lung cancer (NSCLC): A multicentre phase II clinical trial

Abstract A phase II study in patients with stage IIIB/IV non-small cell lung cancer (NSCLC) was carried out to evaluate the clinical activity and toxicity of the chemotherapeutic combination of gemcitabine+vinorelbine (GEM/VNR). Forty-five patients (40 male, 5 female) with a median age of 67 years (range 37–73) and a median ECOG performance status of 1 (range 0–2) were enrolled into the trial. Twenty patients had stage IIIB (two positive supraclavicular nodes and 20 cytologically positive pleural effusion), and 25 had stage IV NSCLC. GEM 1000 mg/m 2 diluted in 250 cc 3 of normal saline was administered iv on days 1, 8, and 15, while VNR was given 30 mg/m 2 on days 1 and 8 every 4 weeks. The…

“Carcinoma mammario metastatico: quali farmaci in seconda linea?”

Mitomycin C plus vindesine plus etoposide (MEV) versus mitomycin C plus vindesine plus cisplatin (MVP) in stage IV non-small-cell lung cancer: A phase III multicentre randomised trial

Purpose : To compare mitomycin C plus vindesine plus etoposide (MEV) vs. mitomycin C plus vindesine plus cisplatin (MVP) in the treatment of stage IV non-small-cell lung cancer. Patients and methods : 204 patients were entered in a phase III multicentre randomised trial from June 1990 to December 1994 and stratified according to the ECOG performance status (0-1 vs. 2). MVP was given in the following dosages : mitomycin C 8 mg/m 2 + vindesine 3 mg/m 2 + cisplatin 100 mg/m 2 i.v. day 1 and vindesine 3 mg/m 2 i.v. day 8 with cycles repeated every 4 weeks. MEV was given in the following dosages : mitomycin C 8 mg/m 2 + vindesine 3 mg/m 2 i.v. day I and etoposide 100 mg/m 2 i.v. days 1 to 3 with…

[Role of loco-regional treatments for patients with breast cancer liver metastases].

“Role of biomarkers in the regulatory process”

“Cisplatin and gemcitabine with either vinorelbine or paclitaxel in the treatment of carcinomas of unknown primary site”

BACKGROUND: : To date, the standard treatment for patients who have carcinoma of unknown primary site has not been established. METHODS: : In this randomized Phase II study, 66 previously untreated patients (33 patients per arm) with carcinomas of unknown primary site received cisplatin (35 mg/m2) and gemcitabine (1000 mg/m2) with either paclitaxel (70 mg/m2) or vinorelbine (25 mg/m2), and all drugs were administered intravenously on Days 1 and 8 of a 21-day cycle. Twenty-nine patients (44%) presented with > or =2 involved sites. The pathologic diagnosis was mainly adenocarcinoma (48 patients; 72.7%) and squamous carcinoma (7 patients; 10.6%). RESULTS: : In the first arm, 16 patients (48.5%…

The effectiveness of the topical use of 0,2% glyceryl trinitrate to decrease post –hemorrhoidectomy pain and to improve wounds healing.

Combined Carboplatin plus Ifosfamide and Cisplatin in Patients with Advanced Ovarian Carcinoma. A Phase I–II Study

Abstract Because of the relative lack of overlapping toxicity, carboplatin (PPL) and cisplatin (CDDP) can be easily combined for treatment of ovarian cancer to increase total platinum dose intensity. Ifosfamide (IFO), one of the most effective single agents in ovarian cancer, has a low hematological toxicity when administered in continuous infusion. From January 1991 to December 1993, 34 patients with advanced ovarian cancer, previously untreated with chemo- or radiotherapy, were enrolled in a phase I–II study with the aim of determining the maximum tolerated dose (MTD) of CDDP (on day 8 of a 28-day cycle) in combination with PPL (300 mg/m 2 on day 1) and IFO (4,000 mg/m 2 /24 h by continuo…

Clinical surrogate end-points

This presentation reflected a personal opinion about the role of surrogates as clinical end-points. According to the Biomarkers Definitions Working Group, a surrogate is ‘a biomarker that is intended to substitute for a clinical end-point and is expected to predict clinical benefit (or harm or lack of clinical benefit) based on epidemiologic, therapeutic, pathophysiologic or other scientific evidence’.1 Although overall survival is the gold standard recognised by both the European Medicines Agency (EMEA) and the US Food and Drug Administration (FDA) as a basis for conditional (EMEA) or accelerated (FDA) approval of new anticancer agents, surrogate end-points are often considered to be reaso…

“Weekly regimen of cisplatin, epirubicin, 5-Fluorouracil and folinic acid with G-CSF is active in advanced gastroesophageal (GE) and gastric (G) cancer: a phase II study”

Progression-free survival as an end-point in clinical trials of biotherapeutic agents

Abstract Progression-free survival (PFS), the time from registration or randomisation of a patient until objective disease progression or death, can be considered as an outcome for clinical research and also as a basis for regulatory approval. Current experience suggests that greater standardisation and consistency are needed for clinical trials utilising PFS endpoints. To this end, the Biotherapy Development Association (BDA) convened a breakout session on the topic of PFS during its Third Alpine Meeting held 14–16 March 2007. Representatives of the pharmaceutical industry, regulatory agencies, academia, and patient advocacy groups identified challenges, developed recommendations, and work…

"Baseline physical functioning status of metastatic colorectal cancer patients predicts the overall survival but not the activity of a front-line oxaliplatin-fluoropyrimidine doublet"

BACKGROUND: No differences in response rate (RR), progression-free survival (PFS), overall survival (OS) and quality of life (QoL) were seen in patients randomly treated with biweekly oxaliplatin plus either fluorouracil/folinic acid or capecitabine. METHODS: We investigated the independent effect of baseline clinical characteristics and physical functioning (PF) domain on RR, PFS, and OS in 310 patients who completed the EORTC QLQ-C30 questionnaire. Multivariate analyses stratified by treatment were performed. An exploratory analysis was done by grouping patients with a PF score superior or equal to the highest quartile (n = 111), included between the highest and the lowest quartiles (n = …

Colorectal Cancer in Elderly Patients: From Best Supportive Care to Cure

Colorectal cancer is one of the major causes of cancer mortality in the elderly population (median age at diagnosis of 71 years) in Western Countries. Moreover patients with metastatic disease are often elderly with significant co- morbidities. Unfortunately, elderly patients are often untreated and under-represented in clinical trials, even if most clinical trials that have included this setting of population have shown similar survival rates and toxicities to younger patients. Age itself should not be considered for candidacy to chemotherapy but it should be taken in consideration the great heterogeneity of co-morbidities present in the elderly population. Therefore, the best treatment st…

Weekly docetaxel in the treatment of metastatic breast cancer

Breast cancer is the most frequent tumor among women worldwide and is the second cause of cancer-related mortality in the US. Metastatic breast cancer (MBC) accounts for less than 10% of newly diagnosed breast cancer patients and about 30% of early breast cancer patients will develop recurrent, advanced, or metastatic disease. It remains an incurable illness and the primary goal of its management is palliative. Several agents are active for the fi rst-line treatment of MBC. The taxanes, paclitaxel and docetaxel, represent the standard of care for the treatment of these patients. Among the various schedules, docetaxel can be administered weekly, achieving similar effi cacy results with lower…

Efficacy and Tolerability of Biweekly Bevacizumab, Irinotecan, Folinic Acid and Fluorouracil Intravenous Bolus (BIFF Regimen) in Patients With Metastatic Colorectal Cancer: The Southern Italy Cooperative Oncology Group Experience

Abstract Background We have extensively assessed a biweekly regimen of irinotecan plus folinic acid and fluorouracil bolus (IRIFAFU) in metastatic colorectal cancer (MCRC). Here, we report on the safety and activity of BIFF (bevacizumab plus IRIFAFU) regimen in 94 mCRC patients. Patients and Methods Bevacizumab 5 mg/kg (1 hour), and irinotecan 180 mg/m 2 (1hour) were given intravenously on day 1, 6S-folinic acid 250 mg/m 2 (2 hours), and fluorouracil 850 mg/m 2 (bolus) were given intravenously on day 2 every 2 weeks for a median of 9 cycles per patient (range, 1-12), and maintenance bevacizumab alone was delivered in 16 cases. Results Grade ≥ 3 hematologic toxicities were neutropenia (50%) …

“Bevacizumab (Bev), irinotecan (IRI), folinic acid (FA), and 5-fluorouracil (FU) every 2 weeks (BIFF regimen) as first-line treatment for metastatic colorectal cancer (MCRC) patients (pts): The SICOG experience”

e15067 Background: The IRIFAFU regimen produced in MCRC pts a consistent activity (RR, 33% [95% CI, 27–39%], PFS, 7.4 [95% CI, 6.5–8.3] mo.) in 2 consecutive randomized SICOG trials . Bev was proven to significantly improve the efficacy of IFL regimen. Here we report the safety and activity results of the BIFF regimen as first-line treatment of MCRC. Patients: From Feb 2007 to Jul 2008, 95 pts with MCRC were treated: so far, 85 pts were evaluated for safety: M/F were 47/38, median age (range) was 64 (35–78) yrs. Fifty-six pts had a colon, and 29 pts a rectal carcinoma. ECOG PS was 0 (63 pts, 74%), or 1 (22 pts, 26%). Thirty-four (40%) pts had 1 site, 33 (39%) 2 sites, and 18 (21%) pts ≥3 s…

“Bevacizumab (Bev) with irinotecan (IRI), folinic acid (FA), and 5-fluorouracil (FU) i.v. every 2 weeks (BIFF regimen) as first-line treatment for metastatic colorectal cancer (MCRC) patients (pts): an observational study of the Southern Italy Cooperative Oncology Group (SICOG)”

Combination chemotherapy with cyclophosphamide, doxorubicin and vincristine in the treatment of stage III-IV small-cell lung cancer.

SummaryTwenty patients with histologically confirmed small-cell lung cancer were treated with cyclophosphamide 1000 mg/m2 i.v. on day 1, vincristine 1.4 mg/m2 i.v. day 1, and adriamycin 50 mg/m2 i.v. on day 1. This protocol was repeated every 21 days. Out of 17 evaluable patients 2 obtained a complete response (12%) with a mean duration of 11 months, 4 patients achieved a partial response with a mean duration of 6.3 + months, and 1 had a minimal response of 7.2 months. Two patients had a stabilization which lasted a mean of 4 + months, while 8 patients progressed. Although the mean survival was higher in responders than in non-responders, the difference in survival time was not statisticall…

“Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer:the IGCS-COL multicentre, randomised, phase III study”

The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2x2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival a…

“Cisplatin (P)-including triplets versus P-free doublets in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC): final results of the SICOG 0101 randomized trial”

“Randomized comparison of capecitabine versus fluorouracil/leucovorin in combination with oxaliplatin in metastatic colorectal cancer patients: Southern Italy Cooperative Oncology Group trial 0401”

Oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer: a multicenter phase II trial of the Southern Italy Cooperative Oncology Group.

Purpose: This phase II trial assessed the tolerability and efficacy of a triplet of oxaliplatin, irinotecan, and fluorouracil/folinic acid in advanced gastric cancer. Methods: Patients with unresectable or metastatic gastric cancer, unexposed to palliative chemotherapy, received oxaliplatin 85 mg/m 2 iv and irinotecan 150 mg/m2 iv on day 1, 6S-folinic acid 250 mg/m2 iv and fluorouracil 750 mg/m2 iv on day 2, every 2 weeks. Response rate (RR) was assessed after a minimum of four cycles, and treatment continued up to 12 cycles. Results: Sixty-three patients were treated, with a median of eight (range 1-12) cycles/patient. Two complete and 19 partial responses were registered (RR 33% [95% CI, …

Vinorelbine and Cisplatin for the Treatment of Recurrent and/or Metastatic Carcinoma of the Uterine Cervix

<i>Background:</i> To test the clinical activity and toxicity profile of the combination regimen of vinorelbine and cisplatin in a series of patients with carcinoma of the cervix uteri with de novo metastatic disease or recurrent disease after previous therapy. The main aims of the study included analysis of objective response rates, toxicity, and time to progression. <i>Patients and Methods:</i> Forty-two eligible patients were enrolled into the trial and treated with cisplatin 80 mg/m<sup>2</sup> on day 1 and vinorelbine 25 mg/m<sup>2</sup> on day 1 and 8. This regimen was repeated every 21 days upon resolution of toxicity for 3 cycles befor…

1308 Evaluating the prognostic role of serum extracellular domain (ECD) of HER-2/neu (s-HER2) in patients (PTS) with metastatic (M) breast cancer (BC): results of an observational study

High-dose folinic acid and 5-fluorouracil plus cisplatin on a weekly schedule in the treatment of advanced cancer of the head and neck

A group of 60 patients with advanced head/neck cancer were treated with high-dose folinic acid (500 mg/m-2/week-1) plus 5-fluorouracil (400 mg/m-2/week-1 on day 1, and cisplatin (20 mg/m-2/week-1) 24 h after folinic acid infusion was completed. Out of 55 evaluable patients, 10 patients (18%) experienced a complete response with a mean duration of 11.4+ months, 25 patients had a partial response (45%) of 6.7+ months, 6 patients (11%) showed a stabilization of 4.8+ months, and 14 (25%) progressed. The overall response rate was 63.6% (95% confidence limits 56.5%-69.5%). Patients pretreated with radiotherapy had a 67% overall response rate, while those pretreated with chemotherapy showed a 54% …

Effect of human granulocyte colony stimulating factor (G-CSF) and reduced glutathione (GSH) on drug-induced leukopenia in golden Syrian hamsters.

Prognostic value of vascular endothelial growth factor (VEGF) and D-Dimer (DD) levels in cancer patients

“Unexpectedly high survival rate in very poor prognosis stage III B breast cancer patients receiving cisplatin-based primary chemotherapy. A multicenter Italian study”

605 Background: Primary chemotherapy, as part of multimodality treatment, has become the standard of care for locally advanced breast cancer (LABC) to increase DFS, OS and conservative surgery. Stage III B is renowned as the worst of LABC, and despite appropriate therapy the majority of patients (pts) will experience distant metastases and death within 2–3 years. The optimal regimen and schedule of primary chemotherapy is uncertain. Aim of our study was to verify the efficacy of an original cisplatin-based regimen (PEV) in terms of response and survival. Methods: Between 1996 and 2001 72 consecutive III B pts were treated with primary chemotherapy: Cisplatin 50 mg/m2, Epirubicin 100 mg/m2, …

“Intensified primary chemotherapy improved the outcome in poorer prognosis LABC T4 patients: results of a multicentric Italian study”

“Biweekly docetaxel (T) and gemcitabine (G) followed by oral vinorelbine as first line treatment of metastatic breast cancer: preliminary results”

“OXXEL (Oxaliplatin plus Xeloda) versus OXAFAFU (Oxaliplatin plus folinic acid-modulated 5-fluorouracil i.v. bolus) every 2 weeks in metastatic colorectal carcinoma (MCC): preliminary safety and activity analysis”

A randomised factorial trial of sequential doxorubicin and CMF vs CMF and chemotherapy alone vs chemotherapy followed by goserelin plus tamoxifen as adjuvant treatment of node-positive breast cancer

The sequential doxorubicin → CMF (CMF = cyclophosphamide, methotrexate, fluorouracil) regimen has never been compared to CMF in a randomised trial. The role of adding goserelin and tamoxifen after chemotherapy is unclear. In all, 466 premenopausal node-positive patients were randomised to: (a) CMF × 6 cycles (CMF); (b) doxorubicin × 4 cycles followed by CMF × 6 cycles (A → CMF); (c) CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years (CMF → GT); and (d) doxorubicin × 4 cycles followed by CMF × 6 cycles followed by goserelin plus tamoxifen × 2 years (A → CMF → GT). The study used a 2 × 2 factorial experimental design to assess: (1) the effect of the chemotherapy regimens (CMF vs A …

“The European Medicines Agency (EMEA) guideline on oncology drug development”

“Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small cell lung cancer: a phase III randomized trial of the Southern Italy Cooperative Oncology Group (SICOG 0101)”

BACKGROUND: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations. PATIENTS AND METHODS: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 5…

“Dose-Dense Primary Chemotherapy, as Part of Multidisciplinary Treatment, for Inoperable Stage III B Breast Cancer - Long-Term Results of a Phase II Trial”

<i>Background:</i> Primary chemotherapy as part of multidisciplinary approach is the established treatment for inoperable stage III B breast cancer. The primary endpoints were conversion to operable disease and feasibility of conservative surgery (breast-conserving therapy: BCT); secondary were clinical and pathological complete response rate, local and distant control and safety of the primary regimen. <i>Methods:</i> Between 1998 and 2001, 40 inoperable breast cancer patients ≤60 years, 72% T4abc and 28% T4d, received 6 cycles of primary PEV dose-dense regimen: cisplatin 50 mg/m<sup>2</sup>, epirubicin 100 mg/m<sup>2</sup> and vinorelbine 25…

Weekly administration of gemcitabine plus docetaxel in patients with advanced breast cancer: a phase 1 study.

<i>Objective:</i> This study was designed to determine the maximum tolerable dose (MTD) of gemcitabine plus docetaxel, both given on a weekly schedule, in patients with pretreated metastatic breast cancer (MBC). <i>Methods:</i> Heavily pretreated patients with MBC, aged 18–75 years with World Health Organization performance status of 0–2 were enrolled. Three escalating weekly doses of docetaxel (30, 35 and 40 mg/m<sup>2</sup>) followed by a weekly fixed dose of gemcitabine, 800 mg/m<sup>2</sup>, were administered on days 1, 8 and 15 of a 28-day cycle. Dose-limiting toxicity (DLT) included grade >3 hematologic toxicity and grade >2 stomat…

“Preliminary results of G > GVIELC: a phase III trial of gemcitabine associated to vindesine or gemcitabine alone in elderly or poor performance patients with advanced non-small cell lung cancer (NSCLC)”

“Serum HER-2/neu (s-HER2) levels evaluation in breast cancer (BC) patients (PTS)”

A Phase II Trial of Mitoxantrone plus Cyclophosphamide and 5-Fluorouracil in Modulation with Levo-Folinate for Advanced Breast Cancer Patients

Advanced breast cancer remains a major clinical problem. Current chemotherapy regimens are able to induce a clinical response in many patients but do not appear to influence significantly patients' survival. The use of new drugs such as mitoxantrone with a predicted lower toxicity and biochemical modulation of 5-fluorouracil with levo-folinate are extensively studied research areas that could combine good therapeutic efficacy with the maintenance of an acceptable quality of life. 34 patients with advanced breast carcinoma were included in the study. Only 4 women had received prior chemotherapy for advanced disease. Treatment plan was: 5-fluorouracil 400 mg/m2 + l-leucovorin 100 mg/m2 days 1…

“Capecitabine or folinic acid/fluorouracil i.v bolus plus eloxatin evaluation (COFFE trial) in metastatic colorectal carcinoma (MCRC): final results of the Southern Italy Cooperative Oncology Group (SICOG) 0401”

Biweekly oxaliplatin plus irinotecan and folinic acid-modulated 5-fluorouracil: a phase II study in pretreated patients with metastatic colorectal cancer.

Oxaliplatin (OXA) and irinotecan (IRI) are active drugs for metastatic colorectal cancer, their toxicity profiles are not overlapping, and both drugs have shown at least additivity with folinic acid-modulated 5-fluorouracil (5FU). We carried out this phase II study to assess the activity and toxicity of a biweekly regimen including OXA plus IRI on day 1, and levo-folinic acid (LFA) plus 5FU on day 2 (OXIRIFAFU) in pretreated patients with metastatic colorectal cancer. Forty-one patients, all previously treated with adjuvant and/or palliative 5FU-based chemotherapy (16 of them already exposed to IRI, OXA or both), were enrolled into this trial. On the basis of sensitivity to previous treatme…

“Erlotinib”

“Final results of a phase II trial of a weekly (W) poly-chemotherapy (CT) with cisplatin (CDDP), epirubicin (EPI), fluorouracil (5FU), folinic acid (FA) and G-CSF for the treatment of gastroesophageal (GE) and gastric (G) cancer (C)”

“Bevacizumab (BEV),irinotecan (IRI), folinic acid (FA) and fluorouracil (FU) every 2 weeks (BIFF regimen) as first-line treatment for metastatic colorectal cancer (MCRC) patients (pts): the Southern Italy Cooperative Oncology Group (SICOG) experience”

Cisplatin and gemcitabine with either vinorelbine or paclitaxel in the treatment of carcinomas of unknown primary site : results of an Italian multicenter, randomized, phase II study.

BACKGROUND. To date, the standard treatment for patients who have carcinoma of unknown primary site has not been established. METHODS. In this randomized Phase II study, 66 previously untreated patients (33 patients per arm) with carcinomas of unknown primary site received cisplatin (35 mg/m2) and gemcitabine (1000 mg/m2) with either paclitaxel (70 mg/m2) or vinorelbine (25 mg/m2), and all drugs were administered intravenously on Days 1 and 8 of a 21-day cycle. Twenty-nine patients (44%) presented with ≥2 involved sites. The pathologic diagnosis was mainly adenocarcinoma (48 patients; 72.7%) and squamous carcinoma (7 patients; 10.6%). RESULTS. In the first arm, 16 patients (48.5%) experienc…

“Results of a phase II study of a weekly regimen of cisplatin (CDDP),epirubicin (EPI), fluorouracil (5FU) and folinic acid (FA) with G-CSF in gastroesophageal (GE) and gastric (G) cancer”

The effectiveness of combination chemotherapy with cisplatinum and etoposide in the treatment of advanced non-small cell lung cancer.

Twenty-one patients with histologically proven advanced or disseminated non-small cell lung cancer were treated with cisplatinum 80 mg/m2 i.v. day 1 and etoposide (VP16) 80 mg/m2 i.v. day 1- greater than 3.15 patients were evaluable for response. One patient (6.6%) achieved a complete response, 4 (26.7%) a partial response and 6 (40.0%) a stabilization of disease. Four patients (26.7%) progressed. An improvement in performance status was obtained in more than 50% of cases. Responders had a mean survival of 345 + days, while non-responders 191.7 days. The treatment was generally well tolerated. In our opinion this combination regimen offers good palliation for patients affected by advanced a…

Vinblastine and interferon-alpha-2a regimen in the treatment of metastatic renal cell carcinoma.

Thirteen patients with histologically proven advanced and/or metastatic renal cell carcinoma (RCC) were treated with vinblastine (Velbe, Eli Lilly, Sesto Fiorentino, Italy) and interferon-alpha-2a (Roferon-A, Roche, Milan). Eleven out of 13 patients were evaluable. Eighteen percent of patients had partial response, 46 % stable disease (SD), and 36 % progressive disease (PD). The mean survival of responders was 228+ days, whereas the patients showing SD and PD had a mean survival of 154+ and 107+ days respectively. Toxicity, including influenza-like syndrome, fever, neurological and gastrointestinal side effects, was generally mild. However, medication with paracetamol was required in 82 % …

A Phase I–II Study on the Toxicity and Therapeutic Efficacy of 5-Fluorouracil in Combination with Leucovorin and Cisplatinum in Patients with Advanced Colorectal Carcinoma

5-Fluorouracil (5-FU) has been the treatment of choice for colorectal carcinoma with an overall response rate of about 20%. Recent studies have shown that folate (LV) can increase 5-FU therapeutic efficacy, achieving about a 40% response rate without a clear impact on survival. Cisplatinum (CDDP) is usually inactive in colorectal carcinoma, but the association with 5-FU results in a synergistic antineoplastic effect. A phase I-II study was done to assess the maximally tolerated dose (MTD) of CDDP in association with 5-FU + LV. The MTD for CDDP was 20 mg/m2/wk in association with 5-FU 400-500 mg/m2/wk and LV 500 mg/m2/wk. WHO criteria were used for evaluation of both toxicity and response. I…

Safety and efficacy of irinotecan plus high-dose leucovorin and intravenous bolus 5-fluorouracil for metastatic colorectal cancer: pooled analysis of two consecutive southern Italy cooperative oncology group trials.

Abstract Background A biweekly regimen of irinotecan 200 mg/m2 on day 1 and levo-leucovorin (LV) 250 mg/m2 plus 5-fluorouracil (5-FU) 850 mg/m2 via intravenous bolus on day 2 was assessed in 2 consecutive randomized trials in metastatic colorectal cancer (CRC). Patients and Methods Individual data of 254 patients were merged, and baseline features potentially affecting overall response rate (ORR), progression-free survival (PFS),overall survival (OS), and occurrence of severe toxicity were analyzed by univariate and multivariate analyses. Results In the pooled series, ORR was 33% (95% confidence interval [CI], 27%-39%). Liver-only disease (47% vs. 25%; P = 0.0012) and absence of previous we…

Cytokine Gene Polymorphisms and Breast Cancer Susceptibility

Human breast cancer (BC) is characterized by a considerable clinical heterogeneity. Steroid hormone receptor expression and growth factor receptor expression have been considered suitable diagnostic and prognostic markers, whereas mutations of oncosuppressor and gatekeeper genes have been found associated with an increased risk for this malignancy. To evaluate the role that polymorphisms of genes involved in the regulation of inflammatory response might play in BC susceptibility, we investigated associations between cytokine functionally relevant polymorphisms in 84 BC patients compared to 110 age- and sex-matched controls. TNF-alpha (-308G/A), TGF-beta1 (+869C/T), IL-10 (-1117G/A; -854C/T;…

A Phase I Study of Cisplatinum plus 5-Fluorouracil in Modulation with Citrovorum Factor in Metastatic Colorectal Carcinoma

A phase I study of 5-fluorouracil 600 mg/m2/week and folinic acid 500 mg/m2/week on day 1 and cisplatin administered weekly on day 2 was carried out on 30 patients with metastatic colorectal carcinoma of which 20 patients were pretreated with 5-fluorouracil. The first group of patients received cisplatin at the dose of 5 mg/m2/week. Cisplatin was then escalated to 10, 15, 20, 25, 30, and 35 mg/m2/week for subsequent groups of patients. Gastrointestinal side-effects were the dose-limiting toxicity. A therapy related death was seen at the dose of 35 mg/m2/week of cisplatin. The maximally tolerated dose of cisplatin in combination with 5-fluorouracil and citrovorum factor is 20 mg/m2/week. The…

Phase II study of mitomycin C, etoposide and vindesine in metastatic stage IV non-small-cell lung cancer.

A total of 72 patients with metastatic stage IV non-small-cell lung cancer (NSCLC) were treated with combination chemotherapy comprising the MEV regimen (mitomycin C, 8 mg/m2 given i. v. on day 1; etoposide, 100 mg/m2 given i.v. on days 1–3; and vindesine, 3 mg/m2 given i.v. on day 1; treatment repeated every 3 weeks). In 64 evaluable patients, the objective response rate was 37% (complete responses, 4.7%; partial responses, 32.3%). The median survival was 7.6 months for all patients. The treatment was very well tolerated. MEV proved to be an active and non-toxic regimen for the treatment of metastatic NSCLC.

“Biweekly oxaliplatin plus capecitabine (OXXEL) versus oxaliplatin plus folinic acid-modulated 5-fluorouracil i.v. bolus (OXAFAFU) in metastatic colorectal carcinoma (MCC): safety interim analysis of a Southern Italy Cooperative Oncology Group (SICOG) phase III trial”

Cis-diamminodichloroplatinum plus a 5-day continuous infusion of 5-fluorouracil in the treatment of locally recurrent and metastatic head and neck cancer patients.

A group of 23 consecutive patients with biopsy-proven advanced or metastatic head and neck cancer were treated with cisplatinum, 100 mg/m2 i.v., on day 1 plus 5-fluorouracil, 1000 mg/m2, in continuous infusion for 5 days. Most patients (87%) had recurrent or metastatic cancer and were previously treated (78%). Out of 21 evaluable patients we obtained a 42% overall response rate (complete + partial responses) with a mean duration of more than 8 months and a 14% minimal response rate. A stabilization of disease was achieved in 28% of cases, while 14% of patients progressed. This response rate, as well as the duration of response, seems to be similar to those obtained in other series comprisin…

Cyclophosphamide plus Epidoxorubicin and 5-Fluorouracil with Folinic Acid as a Novel Treatment in Metastatic Breast Cancer: Preliminary Results of a Phase II Study

Twenty consecutive patients with advanced breast cancer were treated with a combination of cyclophosphamide 600 mg/m2 i.v. on day 1, epidoxorubicin 75 mg/m2 on day 1, and 5-fluorouracil 375 mg/m2 i.v. with folinic acid 200 mg/m2 i.v. on days 1----3. The overall response rate was 60%, with 10% of patients showing a complete response with a mean duration of 11.1 + months, and 50% of patients a partial response of 7.4 + months. A stabilization of 5.2 + months was obtained in 20% of cases, while 20% of patients progressed. The most frequently observed toxicity was leukopenia, while expected mucosal toxicities were rather mild.

Oral tegafur in the treatment of gastrointestinal tract cancers: a phase II study.

Fifty patients affected by histologically confirmed gastrointestinal tract cancer (GTC) were treated with oral tegafur (TG) 1,000 mg m-2 p.o. on days 1-14 repeated after a 14 day interval. Out of 42 evaluable patients seven patients had a partial response (PR. 17%) with a median duration of 20.5 weeks, three had a minimal response (7%) with a median duration of 23.7 weeks, nine showed a stabilisation which lasted a median of 31.3 weeks, and 23 progressed (55%). No response was obtained in patients affected by carcinoma of the pancreas and the hepatobiliary system. All PRs were achieved in patients with metastatic disease to the liver. No response was seen in patients with bone, lung or noda…

Prevalence and treatment of cancer pain in Italian oncological wards centres: a cross-sectional survey.

The aim of this national cross-sectional survey was to draw information on pain prevalence and intensity from a large sample of patients who were admitted to oncologic centres for different reasons and to evaluate the pain treatment and possible influencing factors.A total of 2,655 patients completed the study. Nine hundred and one patients (34%) reported pain.Higher pain levels were observed in inpatients, in the presence of bone metastases, and with low levels of Eastern Cooperative Oncology Group status. The number of patients receiving strong opioids increased with the highest levels of pain. However, a significant part of patients with moderate-severe pain were not receiving appropriat…

Carcinoembryonic Antigen as a Monitor in Breast Cancer

: Carcinoembryonic antigen (CEA) levels were serially determined in 125 patients with breast cancer in order to study the diagnostic and prognostic use of serum CEA levels before and/or after surgery and during treatment with hormonal and chemotherapy. Serum CEA levels were elevated in 15.5% of nonmetastatic patients. Carcinoembryonic antigen increased according to stage (TNM classification); and a direct relationship between positive CEA levels and subsequent recurrence was found. After a three-year postoperative interval a 50% survival rate was exhibited in CEA-positive patients vs an 88% survival rate in those patients found to be CEA negative. There is a definite correlation between the…

“High efficacy of the CHOP + Rituximab association in a case of primary rectal non Hodgkin lymphoma (NHL)”

Non presente

“Analysis of interleukin 10 (IL-10)-1082 G/A single nucleotide polymorphism (SNP) genotypes in breast cancer (BC) patients (pts) and in >95 years old cancer free women"

Should cirrhosis change our attitude towards treating non-hepatic cancer?

Cirrhosis is a major cause of morbidity and mortality and is the end stage of any chronic liver disease. Cancer, a leading cause of death worldwide, is a growing global health issue. There are limited data in the literature on the incidence, prevalence and management of non-hepatic cancers (NHC) in cirrhotic patients. The aim of this brief review was to underline the main concerns, pitfalls and warnings regarding practice for these patients. Survival of patients with compensated cirrhosis is significantly longer than that of decompensated cirrhosis and patients with NHC and in Child-Pugh class C should not be candidates for cytotoxic chemotherapy. It is important before starting cytotoxic c…

"Evaluating the prognostic role of serum extracellular domain (ECD) of HER-2/neu (s-HER2) in patients (PTS) with early (E) breast cancer (BC)”

Phase II study of continuous-infusion high-dose ifosfamide in advanced and/or metastatic pretreated soft tissue sarcomas.

Summary Background Ifosfamide has important activity in pretreated soft tissue sarcomas (STS), and recent data support a clinically significant dose-response relationship for this agent. Administration by continuous infusion and hematopoietic support have rendered dose intensification regimens possible by reducing both hematologic and non-hematologic toxicities. The optimal dose and schedule of ifosfamide when given at high doses remain to be defined. In a previous phase I study, we demonstrated the feasibility of a continuous infusion (c.i.) high-dose ifosfamide (HDI) regimen in the ambulatory setting for patients with advanced solid tumors. The objective of the present phase II study was …

Analysis of interleukin 10 (IL-10) -1082G/A single nucleotide polymorphism (SNP) genotypes in breast cancer (BC) patients (pts) and in >95 years old cancer free women

9656 Background:the anti-inflammatory IL-10 -1082 (G/A) SNP might be associated with different risk for breast tumor development. The -1082GG homozygous genotype is associated with an higher IL-10 ...

“OXXEL (oxaliplatin plus Xeloda) vs OXAFAFU (oxaliplatin plus folinic acid-modulated 5-fluorouracil i.v. bolus) every 2 weeks in metastatic colorectal carcinoma (MCC): preliminary safety and activity analysis of a Southern Italy Cooperative Oncology Group (SICOG) phase III trial”

Combined 5-fluorouracil and recombinant alpha-2a-interferon vs. 5-fluorouracil alone in metastatic colorectal carcinoma: a multicenter randomized study.

Weekly docetaxel in the treatment of metastatic breast cancer

Laura Palmeri, Marina Vaglica, Sergio PalmeriDepartment of Oncology, University of Palermo, Palermo, ItalyAbstract: Breast cancer is the most frequent tumor among women worldwide and is the second cause of cancer-related mortality in the US. Metastatic breast cancer (MBC) accounts for less than 10% of newly diagnosed breast cancer patients and about 30% of early breast cancer patients will develop recurrent, advanced, or metastatic disease. It remains an incurable illness and the primary goal of its management is palliative. Several agents are active for the first-line treatment of MBC. The taxanes, paclitaxel and docetaxel, represent the standard of care for the treatment of these patients…

Cisplatin and vinorelbine in advanced and/or metastatic adenocarcinoma of the endometrium: a new highly active chemotherapeutic regimen.

Summary Purpose To date the systemic treatment of recurrent and/or metastatic adenocarcinoma of the endometrium (EAC), using both chemotherapy and hormonotherapy (HT), is far from satisfactory. The significant activity of vinorelbine (VNR), a relatively new semisynthetic vinca alkaloid, demonstrated in advanced breast cancer, bronchial adenocarcinoma, and in head and neck cancer, prompted us to carry out a phase II trial employing the combination of cisplatin and VNR in a pluri-institutional series of patients with recurrent and/or metastatic EAC. Patients and methods Thirty-five patients affected by recurrent and/or metastatic EAC have been treated with CDDP 80 mg/m2 on day 1 plus VNR 25 m…

F3 the advantage of ultrasound-guided FNA of pleura in the diagnosis of the malignant pleural effusion

“Analysis of serum HER-2/neu levels (S-HER2) in breast cancer (BC) patients (pts)”

“Cisplatin (P)- including triplets versus P-free doublets in the treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC): SICOG 0101 randomized trial”

“Weekly docetaxel (DOC) and Gemcitabine (GEM) as first line treatment for metastatic breast cancer (MBC): results of a multicenter phase II study”

Cisplatinum in combination with 5-fluorouracil and citrovorum factor in the treatment of advanced colorectal carcinoma.

A phase II trial of citrovorum factor, 500 mg/m2/week, plus 5-fluorouracil, 400 mg/m2/week on day 1, and cisplatin, 20 mg/m2/week on day 2, was carried out in a group of 40 patients with metastatic colorectal carcinoma. A partial response with a mean duration of 8.4+ months was achieved in 24% of patients, a minimal response with a mean duration of 5.4 months was obtained in 6% of patients, and a stabilization of 6.2 months was achieved in 41%. Ten patients (29%) progressed. A 38% partial response rate was seen in patients with advanced rectal carcinoma, whereas no response was obtained in patients with colon cancer. Interestingly, 5 partial responses were seen in 12 patients pretreated wit…

“I tumori di origine sconosciuta”

Doxorubicin-docetaxel sequential schedule: results of front-line treatment in advanced breast cancer.

<i>Objective:</i> We conducted a multi-institutional phase II study to evaluate the tolerability and activity of a sequential schedule of treatment with doxorubicin and docetaxel in chemotherapy-naive women with advanced breast cancer. <i>Methods:</i> A total of 73 patients with PS (ECOG) 0–2, aged <70 years and adequate bone marrow, renal, liver and cardiac functions were included in the study (13 stage III B and 60 stage IV). The schedule of administration was doxorubicin 50 mg/m<sup>2</sup> by intravenous (i.v.) 30 min injection on day 1 followed the day after by docetaxel 75 mg/m<sup>2</sup>, by i.v. 60 min infusion. Cycles were repeate…

"Incidence of different KRAS mutation in non-small cell lung cancer (NSCLC) patients, TAILOR STUDY

Investigator-initiated trials of targeted oncology agents: why independent research is at risk?

Background: Drug development traditionally has relied upon the complementary contributions of clinicians and scientists at academic institutions and at pharmaceutical companies. Greater regulatory burdens, increased bureaucratic requirements, restricted reimbursement, and spiralling research and development costs are exerting pressure on the drug development pipeline. The result is a de-emphasis of exploratory research, particularly independent academic research, despite its proven value in identifying new drug targets and developing innovative cancer therapies. Design: An expert panel assembled by the Biotherapy Development Association-a nonprofit international forum for academic and indus…

5-Fluorouracil and recombinant alpha interferon-2a in the treatment of advanced colorectal carcinoma: a dose optimization study

A dose optimization study was carried out with the aim of identifying the maximally tolerated dose of recombinant alpha interferon-2a (raIFN-2a) in combination with 5-fluorouracil (5FU). 5FU was given at the dose of 750 mg/m2 over a 4-hour infusion on day 1- - greater than 5 followed by 750 mg/m2 weekly i.v. bolus. Recombinant aIFN-2a was started at 3 x 10(6) IU subcutaneously three times/week. 12 patients with advanced colorectal carcinoma were included in the study. 10 patients had previously received chemotherapy for advanced disease. Severe fatigue, most likely attributable to rIFN, was the dose-limiting toxicity. The dosage of raIFN-2a could not be further escalated above 12 x 10(6) IU…

Interleukin 3 in the treatment of chemotherapy induced thrombocytopenia.

We enrolled 19 cancer patients (11 females, 8 males) with thrombocytopenia after standard dose of chemotherapy to receive IL3 10 mg/kg/day s.c. until hematologic recovery. Therapeutic success was obtained in 69.6% of cycles; a major response in 39.3% and a minor response in 30.3% of cycles. We obtained the best results in case of platelet count <49,000/mm3. The main toxicity was a flu-like syndrome. In two cycles (6%) we registered allergic episodes with flushing and lipothymia. In the 47% of cycles evaluable for toxicity no side effect was registered.

“Breast conservation therapy as a safe and effective alternative to mastectomy for selected T4 patients treated with primary chemotherapy as part of multimodality approach”

Recombinant human erythropoietin (rhEpo) enhances recovery from cisplatin (CDDP) - induced anemia in golden syrian hamsters

Analisi della frequenza del polimorfismo 1249-1250insACAA del gene TGF-beta2 in un gruppo di pazienti affette da carcinoma della mammella.

“Comparison of the safety and efficacy of paclitaxel plus gemcitabine combination in young and elderly patients with locally advanced or metastatic non-small cell lung cancer. A retrospective analysis of the Southern Italy Cooperative Oncology Group trials”.

We retrospectively assessed tolerability and efficacy of paclitaxel plus gemcitabine combination in 259 patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) enrolled in three randomized SICOG trials according to their age (70 years) at study entry. Apart from age, demographic and clinical characteristics were similar in the two groups. Response rate of paclitaxel plus gemcitabine was similar in younger and in elderly (36% versus 30%). Chemotherapy was well tolerated, but severe neutropenia (12% versus 7%), anaemia (6.6% versus 1.8%), and vomiting (5% versus 0) were more frequent in elderly patients. Both median progression-free survival (PFS, 5.5 months versus 4.2…

“Long-term effect in outcomes of intensified primary chemotherapy in poor prognosis LABC T4 patients: results of a multicenter Italian study”

Modulation of 5-fluorouracil as adjuvant systemic chemotherapy in colorectal cancer: the IGCS-COL multicentre, randomised, phase III study

The aims of this multicentre, randomised phase III trial were to evaluate: (1) the role of levamisol (LEV); and (2) the role of folinic acid (FA), added to 5-fluorouracil (5FU) in the adjuvant treatment of colorectal cancer. Patients with histologically proven, radically resected stage II or III colon or rectal cancer were eligible. The study had a 2x2 factorial design with four treatment arms: (a) 5FU alone, (b) 5FU+LEV, (c) 5FU+FA, (d) 5FU+LEV+FA, and two planned comparisons, testing the role of LEV and of FA, respectively. From March 1991, to September 1998, 1327 patients were randomised. None of the two comparisons resulted in a significant disease-free (DFS) or overall (OAS) survival a…

”L’associazione di gemcitabina e docetaxel nel trattamento del carcinoma mammario metastatico”

“Weekly docetaxel and gemcitabine as first line treatment for metastatic breast cancer: results of a multicenter phase II study”

&lt;i&gt;Objectives:&lt;/i&gt; We conducted a multicenter phase II study to evaluate the clinical efficacy, toxicity, and dose intensity of a new weekly schedule of docetaxel and gemcitabine as first-line treatment of metastatic breast cancer patients. &lt;i&gt;Methods:&lt;/i&gt; We enrolled 58 patients, 52% of whom had received a previous anthracycline-containing chemotherapy. The treatment schedule was: docetaxel 35 mg/m&lt;sup&gt;2&lt;/sup&gt; and gemcitabine 800 mg/m&lt;sup&gt;2&lt;/sup&gt; i.v. on days 1, 8, 15 every 28 days. &lt;i&gt;Results:&lt;/i&gt; All patients were assessable for toxicity and 56 for efficacy. Overall response rate was 64.3% with 16.1% of complete responses and 48…