Phase I-II study of irinotecan in combination with mitomycin C in patients with advanced gastrointestinal cancer.

This phase I-II study was conducted to determine the maximum tolerated dose and optimal schedule of a combination of irinotecan (CPT 11) and mitomycin C (MMC) in a population of previously treated patients with gastrointestinal malignancies. Four cohorts of patients were recruited with MMC given at 8 mg/m2 for the first 3 levels together with irinotecan at 300 mg/m2, 325 mg/m2, and 350 mg/m2; the fourth dose level was given with MMC at 10 mg/m2 and irinotecan at 325 mg/m2. All treatment was repeated at 21-day intervals. The dose-limiting toxicity was hematologic (thrombocytopenia at level 4), and the recommended doses for subsequent phase II studies are MMC 8 mg/m2 with irinotecan 325 mg/m2. Evidence of efficacy was seen at all dose levels examined and justifies further exploration of this combination in a less heavily pretreated patient population.

[Myxoid liposarcoma of the mediastinum]. / Liposarcome myxoïde du médiastin.

We describe a mediastinal myxoid liposarcoma case in a 47-year-old woman who complained of dyspnea. This kind of tumor is rare and becomes symptomatic by compression on mediastinal structures, especially on the respiratory tract. These neoplasms are therefore often voluminous at the time the diagnosis is made. Histopathologic examination is always necessary as much for diagnosis as prognosis. Surgery, whether radical or palliative, obtain the best therapeutic survival results in myxoid liposarcoma of the mediastinum.

European experience with irinotecan plus fluorouracil/folinic acid or mitomycin.

Tremendous progress has been made in the medical treatment of advanced colorectal cancer during the past 2 to 3 years, due to the availability of several new drugs. Of these new agents, irinotecan (CPT-11 [Camptosar]) seems to be one of the most active against advanced colorectal cancer. It is, therefore, a good candidate for combination with the more classic cytotoxic agents for this disease. This article summarizes several European phase I and II studies in which irinotecan has been combined with (1) fluorouracil (5-FU) alone, given as a repeated bolus injection or a protracted infusion; (2) 5-FU modulated by folinic acid (leucovorin) according to different schedules; or (3) mitomycin (Mutamycin). All of these studies have demonstrated clinical responses in patients with advanced colorectal carcinoma, including complete responses. The toxicity profiles of the various combinations seem to be acceptable; neutropenia and delayed diarrhea are the most frequent side effects. Large phase III studies are still warranted to demonstrate the benefit of these irinotecan-based regimens.

Phase I/II study of paclitaxel, cisplatin, and cyclophosphamide in advanced ovarian carcinoma: preliminary results.

In this phase I/II study, we assessed the impact of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in the treatment of advanced ovarian carcinoma combined with the standard regimen cisplatin/cyclophosphamide given as follows: paclitaxel 175 mg/m2 (over 3 hours perfusion with standard premedication), cisplatin 80 mg/m2 (6 to 12 hours after paclitaxel), and cyclophosphamide 400 mg/m2. From February 1994 to January 1996, 27 patients (median age, 55 years; age range, 35 to 74 years) were entered into the study. Eight patients had distant metastases and 19 had early locoregional disease (stage III, 18 patients; stage IC, one patient). Twenty-two patients had undergone prior surgery (simple biopsy, six patients; optimally debulked, nine patients; suboptimally debulked, seven patients). Twenty-one patients had received no prior chemotherapy and six were previously treated with at least one platinum-based regimen. A maximum of six courses of paclitaxel/cisplatin/cyclophosphamide were given every 21 days. Twenty-three patients were evaluable for toxicity: neutropenia (World Health Organization grade 3/4), 91% of patients; thrombopenia (World Health Organization grade 3/4), 13% of patients; two episodes of neutropenia with fever; and neurotoxicity grade 3, 17% of patients. Alopecia grade 3 was reported in all patients. No hypersensitivity reactions and no cardiac toxicity was observed. Among 17 patients evaluable for response (patients with stage IV disease or stage III suboptimally debulked), 12 (70%) clinical complete responses (CRs) and three (18%) partial responses were observed. Among the 12 patients with CRs, 10 underwent second-look laparotomy and seven of them (70%) achieved a pathologic CR. In the group of 11 chemotherapy-naive patients evaluable for response, eight (72%) achieved a CR and three (28%) achieved a partial response. This combination seems to be safe, with very acceptable toxicity, and also seems to be highly active in the treatment of patients with advanced ovarian carcinoma.