0000000000505795
AUTHOR
Youcef M. Rustum
The role of drug sequence in therapeutic selectivity of the combination of 5-fluorouracil and cis-platin.
The therapeutic efficacy of 5-fluorouracil (FUra) and cis-dichlorodiamine-platinum (cis-DDP) in mice bearing transplantable leukemia and solid tumors was evaluated using different sequences of combination of these agents. The optimal sequence was cis-DDP administered 24 h after FUra. The administration of FUra at its maximally tolerated dose (MTD) followed 24 h later by low doses of cis-DDP yielded less toxicity and higher response rate against L1210 and colon 26 than the administration of these two agents in the opposite sequence or concurrently at the MTD. The sequence of administration of these two agents was not therapeutically important when the antitumor activity was evaluated against…
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…
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…
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…