Clinical activity and benefit of irinotecan (CPT-11) in patients with metastatic colorectal carcinoma pre-treated with fluorouracil-based chemotherapy.

The purpose of this prospective study was to assess the efficacy, clinical benefit and safety of irinotecan (CPT-11) in patients with 5-fluorouracil-resistant metastatic colorectal cancer (CRC). Sixteen patients with World Health Organization (WHO) performance status < or = 2 were treated with CPT-11 350 mg/m2 every 3 weeks. The observed partial response (PR) rate was 6.3 per cent with a high rate of stable disease (SD) (43.7%) which was of long duration (21.1 weeks for the best response; 1PR, 7SD). The median survival time for the 16 patients entered into this study was 69.6 weeks. There was no toxic death. The most frequent adverse events were neutropenia (31% grade 3/4) and delayed diarrhea (9.7%). CPT-11 has definite activity in the treatment of progressive metastatic CRC truly resistant to 5-FU which translated into clinical survival benefit. Median survival from first administration of CPT-11 was 78.6 weeks for patients with best response (PR + SD) compared with 28.1 weeks for patients with progressive disease (PD) (P = 0.01). With the appearance of new active drugs in this highly chemotherapy-resistant disease, the definition of response should be reassessed in CRC.

Effects of paclitaxel and carboplatin on quality of life and survival in patients with advanced non-small-cell lung cancer.

The purpose of this phase II study was to determine the effects of paclitaxel plus carboplatin administered by short duration on response rate, toxicity, and quality of life (QOL) in patients with non-small cell lung cancer (NSCLC). Twenty-seven patients were enrolled in this study. The objective response rate was 48.2 per cent, grade 3 or 4 granulocytopenia and thrombocytopenia were observed in 22 per cent and 1.6 per cent, respectively. QOL was assessed in nineteen patients who completed six cycles of chemotherapy. Quality of Life Index (QLI) after six cycles of treatment showed no significant change from the baseline QOL. Compliance with the QOL protocol in this study diminished with the course of chemotherapy which is comparable to the literature figure. Thus, withholding current effective chemotherapy in patients with NSCLC with good performance status is no longer justified.

Phase II study of concurrent chemoradiotherapy for inoperable (bulky) stage III (A/B) non-small cell lung cancer (NSCLC): a preliminary report.

We designed a phase II study to determine the feasibility and toxicity of concomitant radiotherapy and Paclitaxel/Carboplatin followed by adjuvant chemotherapy of the same regimen in patients with newly diagnosed inoperable stage III A/B non-small cell lung cancer. Patients were irradiated with a total dose of 66 Gy. Weekly courses of Paclitaxel 45 mg/m2 and Carboplatin AUC 2 were administered intravenously during the irradiation period. After completion of concurrent chemoradiotherapy, adjuvant chemotherapy with Paclitaxel 175 mg/m2 and Carboplatin AUC 6 intravenously every 3 weeks for 4 cycles were given. Since March 1998, 15 patients have been enrolled. All patients were assessable for efficacy and toxicity after concurrent chemoradiotherapy. Eleven patients were assessable for efficacy and toxicity after adjuvant chemotherapy. After concomitant chemoradiotherapy, complete response (CR) was documented in 2 of 15 (13%). Partial response (PR) was documented in 9 of 15 (60%). After completion of adjuvant chemotherapy in 11 patients, the overall response rate was 91 per cent. (18% CR, 73% PR). There were 8 per cent gr. 3-4 neutropenia which occurred during adjuvant chemotherapy. Concomitant Paclitaxel/Carboplatin and radiotherapy are promising modalities in the treatment of inoperable stage III A/B non-small cell lung cancer.

Paclitaxel and carboplatin in combination in the treatment of advanced non-small-cell lung cancer (NSCLC): a preliminary study.

This study was aimed to determine the activity and toxicity of combination paclitaxel and carboplatin in stage III B and IV NSCLC. Eligibililty required performance status. Paclitaxel was administered at a dose of 200 mg/m2, 3-hour infusion, followed by carboplatin at a tartgeted area under the concentration-time curve (AUC) of 6. Treatment was repeated at 3-week intervals for 6 courses. G-CSF 5 micrograms/kg was subcutaneously injected during subsequent courses if there was grade 3-4 leukopenia or granulocytopenia in the previous course. From August 1996 through June 1997, 15 patients were enrolled. The median age was 47 years (range 20-68 years), 60 per cent were female. 73.3 per cent had adenocarcinoma, and 66.7 per cent had stage III B disease. Eighty three courses were administered; 13 patients (86.7%) completed all six cycles. The objective response rate was 53.3 per cent, with 1 (6.7%) complete response and 7 (46.7%) partial responses. Pleural effusion, lung lesion and lymph node were the three most common sites that responded to chemotherapy. The major toxicity was myelosuppression. Grade 3 or 4 granulocytopenia, anemia and thrombocytopenia were observed in 18 per cent, 7.2 per cent and 1.2 per cent, respectively, of 83 courses administered. Four episodes of febrile neutropenia (4.8%) occurred in 3 patients. There was one episode of anaphylaxis during Paclitaxel infusion. Other common toxicities were mild myalgia, paresthesias, alopecia and fatigue. Most of the toxicities showed cumulative effect. Paclitaxel plus carboplatin is a moderately active regimen in advanced NSCLC. Toxicities of this regimen are well tolerated.