0000000000134245
AUTHOR
Antonio Testa
Treatment of advanced adenocarcinomas of the exocrine pancreas and the gallbladder with 5-fluorouracil, high dose levofolinic acid and oral hydroxyurea on a weekly schedule. Results of a multicenter study of the Southern Italy Oncology Group (G.O.I.M.).
BACKGROUND To date there is no established chemotherapeutic treatment for patients with unresectable locally advanced and/or metastatic carcinomas of the exocrine pancreas or the gallbladder. A multicenter Phase II trial has been performed by the Southern Italy Oncology Group with the aim of evaluating the clinical effectiveness and tolerability of weekly 5-fluorouracil (5-FU) in modulation with intravenous (i.v.) high dose levofolinic acid and oral hydroxyurea. METHODS A total of 70 patients fulfilling the standard eligibility for a Phase II study were enrolled in the trial. Forty patients had advanced pancreatic adenocarcinoma and 30 had advanced gallbladder carcinoma. The treatment sched…
Weekly Levofolinic Acid and 5-Fluorouracil Plus Hydroxyurea in Metastatic Gastrointestinal Adenocarcinomas
There were 42 patients with advanced gastrointestinal carcinomas (GA) enrolled in the study. In the Phase I part of the study we identified the MTD of 5-fluorouracil (5FU) in combination with levofolinic acid 100 mg/m2 per week intravenously plus hydroxyurea 1 g/m2 per week given by mouth in 3 refracted doses starting 6 hours after 5FU was administered. This treatment was given weekly for 6 consecutive weeks followed by a 15-day rest period. We were not able to increase 5FU weekly dosage above 700 mg/m2 due to the occurrence of grade 3-4 gastrointestinal toxicity. Thus 5FU was employed at 600 mg/m2 per week for the Phase II part of the study. Among 20 evaluable patients with measurable meta…
Subcutaneous octreotide versus oral loperamide in the treatment of diarrhea following chemotherapy
Forty patients with chemotherapy-related diarrhea were randomized to receive (i) octreotide 0.5 mg three times per day s.c. or (ii) loperamide 4 mg three times per day p.o. until complete remission of diarrhea was achieved. In the octreotide group 80% of patients showed complete resolution of loose bowel movements within 4 days of therapy, while in the loperamide group this goal was obtained in only 30% of cases (p < 0.001). If after 4 days no benefit was seen, patients were considered to have failed antidiarrheal therapy. Failure was recorded in only one case (5%) treated with s.c. octreotide and in five patients (25%) who received loperamide. The mean duration of antidiarrheal therapy nec…
Pegylated Liposomal Doxorubicin with Vinorelbine in Metastatic Breast Carcinoma
A multicenter phase I-II trial was carried out with the aim of identifying the dose-limiting toxicity and the maximum tolerated dose of vinorelbine (VNR) in combination with pegylated liposomal doxorubicin at a dose of 20 mg/m<sup>2</sup> every 15 days in patients with metastatic breast carcinoma. In the phase I part of the trial, VNR was given at a dose of 20 mg/m<sup>2</sup> every 15 days to a group of 3 patients. In absence of unacceptable toxicity, VNR was escalated to 25, 30, and 35 mg/m<sup>2</sup> for subsequent groups of 3 patients, until the dose-limiting toxicity was reached. No case of palmar-plantar erythrodysesthesia was recorded in these pat…
Vinorelbine plus cisplatin in recurrent or previously untreated unresectable squamous cell carcinoma of the head and neck
Despite considerable progress achieved in the management of head and neck carcinomas (HNC) in the last decade, the prognosis of patients with advanced squamous cell HNC is still dismal. On the basis of the reported good activity of a new vinca alkaloid derivative, i.e., vinorelbine (VNR), we tested the combination of cisplatin and VNR in a series of patients with recurrent or previously untreated unresectable squamous cell HNC. Thirty-five patients with recurrent or previously untreated unresectable squamous cell HNC were treated with a combination of cisplatin 80 mg/m2 on day 1, plus vinorelbine 25 mg/m2 i.v. push on days 1 and 8. This cycle was repeated every 3 weeks. Analysis of response…
A prospective evaluation of the activity of human granulocyte-colony stimulating factor on the prevention of chemotherapy-related neutropenia in patients with advanced carcinoma
After informed consent, 86 patients with advanced cancer undergoing potentially myelosuppressive cytotoxic chemotherapy were randomized to receive placebo or subcutaneous granulocyte - colony stimulating factor (G- CSF) 5 μg/Kg/day in order to prevent severe neutropenia and its related morbidity. The incidence of neutropenia (absolute neutrophil count <1, 000/mm3) was significantly reduced in patients receiving G-CSF than in controls (18% versus 42%; P <0.05). The duration of neutropenia was also shortened by the administration of G-CSF (4.8 versus 8.2 days; P <0.05). Therapy with G-CSF has also a positive impact on the dose-intensity of employed regimens. Patients treated with G-CSF showed…
Methotrexate, Vinblastine, Epidoxorubicin, and Bleomycin as Second-Line Chemotherapy for Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck
Thirty evaluable patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck region previously treated with cisplatin-based chemotherapy were treated with a combination of methotrexate, vinblastine, epidoxorubicin, and bleomycin as second-line chemotherapy. Besides surgery and/or radiotherapy all patients had previously received chemotherapy as induction therapy or as palliation for recurrent disease. Only 20% of patients achieved a partial objective response with a mean duration of 5.6 months (range 3.2-6.2), and 30% of patients had a stabilization of disease with a mean duration of 4.2+ months (range 3.8-6.0). Patients who responded had rhinopharyngeal carcinoma…
A pilot study of vinorelbine on a weekly schedule in recurrent and/or metastatic squamous cell carcinoma of the head and neck.
Vinorelbine (VNR), 5′-nor-anhydrovinblastine, is a new semi-synthetic vinka alkaloid with selective affinity for mitotic microtubules, which has been shown to be active against several non small cell lung cancer lines in vitro [1]. VNR has been reported to yield a 34.7 % and 20 % overall response rate in patients with squamous cell lung carcinoma and bronchial adenocarcinoma respectively [2]. Moreover, VNR has been shown to be active in advanced breast carcinoma where it may induce a 30–50 % response rate depending on the extent of pretreatment [3]. We tested the activity and toxicity of single agent VNR given on a weekly schedule in a series of patients with recurrent and/or metastatic squ…
Mitomycin 'C' and vinorelbine as second line chemotherapy for metastatic breast carcinoma
Aims and background Patients with metastatic breast carcinoma resistant to first line chemotherapy may require further treatment. Results o second line chemotherapy are still largerly unsatisfactory. For this reason a phase II study on the combination of mitomycin C and vinorelbine was carried out. Methods Forty patients with anthracycline pretreated metastatic breast cancer were treated with a combination of mitomycin C 10 mg/m2 i.v. on day 1, and vinorelbine 25 mg/m2 i.v. on days 1 and 8. This cycle was repeated every 28 days. Responses were evaluated according to the WHO criteria. Results A major objective response was recorded in 16 cases (40%; 95% confidence limits 32%-48%), with 2 pat…
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…
Neo-adjuvant chemo-(immuno-)therapy of advanced squamous-cell head and neck carcinoma: a multicenter, phase III, randomized study comparing cisplatin + 5-fluorouracil (5-FU) with cisplatin + 5-FU + recombinant interleukin 2
We carried out an open, randomized, phase III, multicenter clinical trial to compare, in neo-adjuvant setting, the clinical response and toxicity of the combination chemotherapy cisplatin + 5-FU with the same combination plus s.c. recombinant interleukin-2 (rIL-2) in patients with advanced (stage III IV) head and neck squamous-cell carcinoma (HNSCC). Regimen A was the classical Al Sarraf treatment: 100 mg/m2 cisplatin i.v. on day 1 plus 1000 mg m(-2) day(-1) 5-FU on days 1-5 as a continuous infusion. Regimen B was the same as regimen A plus 4.5 MIU/day rIL-2 s.c. on days 8-12 and 15-19. Treatment was repeated every 3 weeks for three cycles. A total of 33 patients were enrolled in the study;…
Hydroxyurea modulates 5-fluorouracil antineoplastic activity in advanced head and neck carcinoma pretreated with chemotherapy
After informed consent 21 patients with advanced head and neck cancer resistant to folinic acid/5-fluorouracil (FA/5FU + cisplatin) were treated with weekly FA/5FU plus low dose hydroxyurea (HU) to evaluate if HU could further modulate 5FU antineoplastic activity. Five patients achieved a partial response (23.8%) which was short-lived (mean duration 6.5 months). Three patients (14%) had stable disease and 13 (62%) progressed. Among responders, four patients had epidermoidal carcinoma and one had clear cell carcinoma. Treatment was well tolerated and 5FU-related toxicity was not apparently worsened by the addition of HU. The most frequent toxicities were nausea/vomiting (81%), diarrhea (52%)…
Weekly 5-fluorouracil and folinic acid plus escalating doses of cisplatin with glutathione protection in patients with advanced head and neck cancer.
Twenty-two patients with advanced head and neck carcinoma were treated with 5FU 400 mg-2 m-1 week and folinic acid 500 mg m-2 week-1 plus CDDP in escalating doses from 20 to 40 mg m-2 week-1 without forced diuresis. Reduced gluthatione at the dose of 1.5 g m-2 was employed to protect patients from CDDP-related nephrotoxicity. The aims of the study were: a) to evaluate the therapeutic efficacy of this schedule, and b) to evaluate reduced gluthatione as uroprotector. Out of 20 evaluable patients 14 (70 %) had a major objective response. A CR with a mean duration of 9.0+ months was achieved in 15 % of the patients, a PR of 5.8+ months in 55 % of the patients, while 3 patients had stable diseas…
Combination chemotherapy of 5-fluorouracil, epidoxorubicin and mitomycin C in the palliative treatment of locally advanced and/or metastatic adenocarcinoma of the stomach
Thirty-seven consecutive patients with advanced and/or metastatic gastric adenocarcinoma received a combination of 5-fluorouracil 600 mg/m2 on days 1, 8, 29, 36; epidoxorubicin 75 mg/m2 i.v. on days 1, 29; mitomycin C 10 mg/m2 i.v. on day 1. This cycle was repeated every 8 weeks. Out of a total of 34 evaluable patients, 2 (5.8%) had a complete response and 7 (20.6%) had a partial response with an overall median duration of 40 weeks (range 20-128). The median survival of responding patients was not reached after a mean follow-up of 76 weeks, while that of patients with no change and progressive disease was reached at 36 and 13 weeks respectively. Treatment was generally well tolerated with h…
Ondasetron versus granisetron in the prevention of chemotherapy‐induced nausea and vomiting. Results of a prospective randomized trial
Background. A single‐institution, prospective, randomized open trial was performed to compare ondansetron and granisetron in the prevention of chemotherapyrelated nausea and vomiting. The effect of antemetic drugs was analyzed indipendently for patients treated with highly emetogenic chemotherapy (Study 1), and those treated with moderately emetogenic regimens (Study 2). Methods. In Study 1. 182 patients treated with chemotherapeutic regimens containing high dose cisplatin (more than 70 mg/m2) were randomized to receive 24 mg of ondasentron intravenously (i. v.) or 3 mg of granisetron i. v. for the control of acute emesis. Patients treated with fractionated chemotherapy and those followed‐u…
ELF regimen in advanced gastrointestinal malignancies: An analysis of its clinical effectiveness and toxicity
A multi-institutional phase 11 study of the combination of levofolinic acid 100 mg/m2, VP16 120 mg/m2 and 5-fluorouracil 500 mg/m2 for 3 consecutive days was carried out on a series of 73 evaluable patients with low performance status affected by locally advanced and/or metastatic gastrointestinal carcinomas. Site of primary tumor were: stomach 26, large bowel 20, pancreas 16, gall-bladder 5, and liver 6. Among patients with gastric carcinoma, 2 patients (8%) had a complete response with a mean duration of 6.8+ months, and 9 (35%) had a partial response with a mean duration of 5.8+ months, for an overall response rate of 43%. Overall response rate was largely unsatisfactory in colorectal ca…
Treatment of recurrent and/or metastatic squamous cell head and neck carcinoma with a combination of vinorelbine, cisplatin, and 5-fluorouracil: a multicenter phase II trial.
Summary Purpose Vinorelbine has been demonstrated to be active against squamous cell carcinomas of the headneck (SCHNC) and lung. This multicenter phase II trial was carried out to evaluate the activity and tolerability of the combination of vinorelbine, cisplatin, and 5-fluorouracil given on an outpatient schedule in a series of 80 patients with recurrent SCHNC. Patients and methods Eighty patients with recurrent and/ or metastatic SCHNC were treated with a combination of CDDP 80 mg/m2 on day 1, 5-FU 600 mg/m2 as a 4-hour infusion on days 2-5, and vinorelbine 25 mg/m2 on days 2 + 8. This cycle was repeated every 28 days. Most patients had oral cavity, larynx, or oropharynx carcinoma (88%).…
A phase I-II study of cyclophosphamide, epidoxorubicin, levofolinic acid/5-fluorouracil and recombinant human granulocyte colony stimulating factor in metastatic breast carcinoma.
Thirty patients with measurable metastatic breast carcinoma were treated with a combination of cyclophosphamide 600 mg/m2 on day 1, levofolinic acid 100 mg/m2 plus 5-fluorouracil 375 mg/m2 on days 1-3, and epidoxorubicin (EDXR) in three refracted doses on days 1-3 with G-CSF rescue for 10 days. In the phase I part of the study, groups of 3 patients received EDXR 20, 25, 30, 35, and 40 mg/m2/day until the dose limiting toxicity (DLT) was reached. At the dose of 40mg/m2/day prolonged grade 4 leukopenia, severe proctitis, and grade 3 diarrhea represented the DLT. All subsequent partients were treated at the maximal tolerated dose of EDXR (35 mg/m2/day). In the group of 18 patients treated at 3…
Cisplatin and epirubicin plus oral lonidamine as first-line treatment for metastatic breast cancer: A phase II study of the Southern Italy Oncology Group (GOIM)
Lonidamine (LND) is a unique antineoplastic drug derived from indazole-3-carboxylic acid which inhibits oxygen consumption and aerobic glycolysis, interfering with energy metabolism of neoplastic cells. LND has been experimentally shown to potentiate the cytotoxic effects of epirubicin (EPI) in human breast cancer cell lines, cisplatin activity in both platinum-sensitive and -resistant human ovarian carcinoma cell lines, and EPI antineoplastic activity in some recent phase III trials carried out in advanced breast cancer. A multicenter phase II trial was carried out with the combination of cisplatin 60 mg/m2, EPI 100 mg/m2 and LND 450 mg/day p.o. in three refracted doses/day starting 2 days…
1206 Comparison of granisetron vs ondansetron vs tropisetron in the prophylaxis of acute nausea and vomiting induced by highly emetogenic chemotherapy (high-dose cisplatin) for treatment of primary head and neck cancer: An open cross-over randomized controlled trial (RCT)
A two-centre prospective randomized open cross-over study to compare granisetron (Gra) vs ondansetron (Ond) vs tropisetron (Tro) in the prevention of high-dose cisplatin-induced nausea and vomiting was carried out. The notable characteristics of our study were: all patients were very homogeneous for tumor site (head and neck cancer), all were treated with high-dose (80 to 100 mg/sqm) cisplatin on day 1 and all were chemotherapy-naive. 141 patients for a total number of 541 chemotherapy cycles containing high-dose cisplatin were randomized to receive 24 mg of Ond intravenously (i.v.) or 3 mg of Gra i.v. or 5 mg of Tro i.v. for the control of acute nausea and emesis. In the Gra group in 138 o…
Epirubicin, Folinic Acid, Fluorouracil, and Etoposide in the Treatment of Advanced Gastric Cancer
In the authors' previous experience, the addition of epidoxorubicin to the FA-FU regimen obtained a better response rate than that of FA-FU alone in patients with advanced gastric cancer. Furthermore, considering the good efficacy and mild toxicity observed with the addition of etoposide to the FA-FU combination in the German study, the authors conducted a trial to explore the efficacy and tolerability of the ELFE regimen (epirubicin, folinic acid, fluorouracil, and etoposide) in previously untreated advanced gastric cancer patients. Of the 55 patients entered, 51 were evaluable for efficacy. Four complete responses (8%) and 21 partial responses (41%) were observed, with an overall response…
Oral granisetron with or without methylprednisolone versus metoclopramide plus methylprednisolone in the management of delayed nausea and vomiting induced by cisplatin-based chemotherapy. A prospective randomized trial.
Background. A single-institution, randomized open trial was prospectively performed to compare orally administered granisetron with or without intramuscularly administered methylprednisolone to metoclopramide plus methylprednisolone in the prevention of delayed nausea and vomiting induced by cisplatin-based chemotherapy. The effects of antiemetic treatments were evaluated from days 2 to 5 of the first cycle after cisplatin administration among patients who had never before received chemotherapy. Methods. All patients were treated with chemotherapeutic regimens containing cisplatin greater than or equal to 80 mg/m 2 and received antiemetic therapy with granisetron 3 mg intravenously for the …
Subcutaneous low-dose interleukin-2 and intravenous 5-fluorouracil plus high-dose levofolinic acid as salvage treatment for metastatic colorectal carcinoma.
Thirty-three consecutive patients with recurrent and/or metastatic colorectal carcinoma (CRC) refractory to previous chemotherapy have been treated with levofolinic acid (I-FA) 100 mg/m2 i.v. over 1 h infusion followed by 5-fluorouracil (5-FU) 600 mg/m2 i.v. bolus every week for 6 weeks followed by a 2 week interval. Patients also received rIL-2 s.c. at 3 MU daily from day 1 to day 5 of each week for at least four consecutive weeks per cycle. Enrolled patients were divided in two groups: (i) group 1 including patients with progressive tumor refractory to chemotherapy with I-FA + 5-FU given for metastatic disease and (ii) group 2 consisting of patients with diagnosis of metastatic disease wi…
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…
Etoposide, doxorubicin (Adriamycin) and cisplatin regimen in advanced gastric adenocarcinoma: experience with a lower dose schedule
A phase II trial of etoposide (100 mg/m2) on days 4, 5, 6, doxorubicin (Adriamycin, 20 mg/m2) on days 1, 7, and cisplatin (30 mg/m2) on days 2, 8 (EAP) was carried out in order to reduce toxicity associated with a full-dose EAP regimen for advanced and/or metastatic gastric adenocarcinoma. Out of 21 evaluable patients, 2 (10%) had a complete response (CR), 7 (33%) had a partial response (PR), 4 (20%) showed no change and 8 progressed (38%). The mean duration of response (CR+PR) was 8.4+ months. Survival of the whole group was 7.5+ months. Treatment was quite well tolerated by most patients on an outpatient basis. Grade 3 vomiting and leukopenia were seen in 30% and 35% of cases respectively…
A Phase II Study of Levofolinic Acid and 5-Fluorouracil Plus Cisplatin in Patients with Advanced Head and Neck Squamous Cell Carcinoma
Forty patients with advanced squamous cell carcinoma of the head and neck (SCHNC) were treated with a combination of levofolinic acid 100 mg/m2+5-fluorouracil 375 mg/m2 in a 4-hour infusion plus cisplatin 20 mg/m2 in a 2-hour infusion for 5 consecutive days, repeated every 21-28 days. In the group of 20 previously untreated patients, a 90% overall response rate (ORR) with a 30% complete response rate (CRR) was obtained. In the group of 20 pretreated patients with recurrent and/or metastatic SCHNC, a 55% ORR with 15% CRR was achieved. This treatment was given on an outpatient basis and was generally very well tolerated with only 2 patients requiring hospitalization. Grade 1-2 gastrointestina…