Phase II trial of fortnightly irinotecan (CPT-11) in the treatment of colorectal cancer patients resistant to previous fluoropyrimidine-based chemotherapy.

INTRODUCTION: This phase II study investigated the anti-tumour activity and toxicity of CPT-11 (250 mg/m2 i.v. infusion over 60 minutes) administered every 2 weeks as second-line chemotherapy in patients with advanced colorectal cancer (CRC). MATERIAL AND METHODS: Patients (n = 63) with histology diagnosis of advanced CRC and proven resistance to previous fluoropyrimidine therapy were enrolled. RESULTS: A total of 510 CPT-11 cycles were administered, with a mean of 8 cycles per patient (range: 1-32). The median relative dose intensity was 93%. Partial response (PR) was obtained in 11 patients (17.5%; 95%CI: 8.1%-26.7%) and 29 patients (46.0%) showed stable disease (clinical benefit of 63.5%). The median duration of response was 6.8 months (95%CI: 6.1-7.5 months), median survival was 8.8 months (95%CI: 6.3-11.5 months) and median time to disease progression was 4.5 months (95%CI: 3.9-5.0 months). Overall, this schedule of CPT-11 chemotherapy was well tolerated by the patient. Neutropenia was the most frequent grade 3/4 haematological toxicity (20.6% of patients and 4.1% of cycles). Neutropenia with concurrent fever or infection occurred in 7 patients (11.1%). Late onset diarrhoea was the most frequent grade 3/4 non-haematological toxicity (19.0% of patients and 2.3% of cycles). Other, lower-incidence, toxicities were anaemia, fever, infection, mucositis, nausea and vomiting. There were no toxic deaths. CONCLUSIONS: We found that CPT-11, administered as 250 mg/m2 i.v. infusion over 60 minutes every 2 weeks, was active and well tolerated schedule in the second-line chemotherapy of advanced CRC patients. This bi-weekly scheme could be used as an alternative to the weekly or the every-three-week schedule as well as in combined therapies with other chemotherapeutic agents for the treatment of advanced, metastatic, CRC.

A phase II trial of fixed-dosed rate gemcitabine in platinum-resistant ovarian cancer: a GEICO (Grupo Español de Investigación en Cáncer de Ovario) Trial.

OBJECTIVES: Gemcitabine has well-recognized activity in the treatment of ovarian cancer. Fixed-dose rate (FDR) delivery has been proposed as a more rationale way to administer gemcitabine, to avoid saturation of the enzyme that catalyzes its intracellular transformation into the active metabolites, difluorodeoxycitidine biphosphate, and triphosphate. Our aim was to assess clinical activity of gemcitabine delivered by FDR infusion in patients with platinum resistant ovarian cancer. MATERIALS AND METHODS: Patients with platinum-resistant ovarian cancer received gemcitabine 1000 mg/m(2) over 120 minutes on days 1 and 8 of each cycle. Cycles were repeated every 3 weeks, and up to 6 cycles were delivered. RESULTS: Forty-eight patients were included in the study. Among 41 patients evaluable for response, 9 clinical responses (1 complete response and 8 partial responses) were observed, achieving a global response rate of 22%. Grade 3 to 4 hematological toxicity consisted of anemia (15% of patients), neutropenia (24%), and thrombopenia (10%). One patient died due to septic shock. The main grade 3 to 4 nonhematological toxicity was asthenia (7 patients, 17%). CONCLUSION: Activity of gemcitabine administered by FDR infusion in patients with platinum-resistant ovarian cancer seems similar to that achieved using 30-minute infusions, with higher toxicity.