Gemcitabine plus vinorelbine in advanced non-small cell lung cancer: a phase II study of three different doses. Gem Vin Investigators.

Our aim was to study the activity and toxicity of the gemcitabine plus vinorelbine (Gem Vin) combination and to identify the optimal dose. Previously untreated patients aged < 70 years, with stage IV or IIIb (not candidates for radiotherapy) non-small cell lung cancer were eligible. Studied dose-levels of Gem Vin, administered on days 1 and 8 every 3 weeks, were (mg m(-2)): level I = 1000/25; level II = 1200/25; level III = 1000/30; level IV = 1200/30. A feasibility study was performed at each dose-level, followed by a single-stage phase II study. Dose-level IV was unfeasible because of grade 4 neutropenia. Overall, out of 126 patients enrolled in phase II studies, there were one complete and 32 partial responses (response rate 26%: 95% CI 18-34%). Response rates were 27.9%, 21.4% and 29.3% at levels I, II and III, respectively. The treatment was well tolerated. Toxicity was less frequent and severe at level I. Overall median survival was 33 weeks (95% CI 28-40). Descriptive quality of life analysis showed that patients with a worse baseline global health status score tended to drop out of the study earlier than those with a better score. Gem Vin is feasible at different doses. It is sufficiently active and well tolerated. A phase III study to compare the effect on quality of life of Gem Vin (level I) vs cisplatin-based chemotherapy is ongoing.

Subcutaneous administration of interleukin-2 and interferon-alpha 2b in advanced renal cell carcinoma: long-term results.

Clinical data have supported the combination of subcutaneous r-interleukin-2 (rIL-2) and r-interferon-alpha (rIFN-alpha) as a promising combination for advanced renal cell carcinoma (RCC), with a reduced toxicity. We evaluated the activity and safety of this outpatient immunotherapy and report on the clinical results and the long-term survival analysis. Objective responses was observed in 9 of 50 (18%) patients, 6 of whom (12%) achieved a complete response. Overall median survival is 12 months, six patients were surviving at a median follow-up of 24 months, and three (6%) are still progression-free.

Salvage chemotherapy with paclitaxel in platinum-resistant advanced ovarian cancer patients.

Encouraging results with Paclitaxel are reported in ovarian cancer patients relapsing and progressing after platinum-based chemotherapy; however, the two populations have different probabilities of a response to a second-line treatment. Here we report the results achieved in 39 patients with platinum-refractory ovarian cancer, treated with Paclitaxel 175 mg/qm2 (or 135 mg/m2 if heavily pretreated) using 3-hour intravenous infusion every 3 weeks, in an attempt to verify the activity of this drug in platinum-resistant patients. The toxicity was mild to moderate and primarily hematologic and neurologic. The objective response rate is 12.8% with no complete responses. The response duration was brief and the median survival 6 (range 1-17) months. An accurate cost-benefit balance is necessary before routinely use of Paclitaxel in platinum-refractory patients. Further research is needed to determine the optimal role of Paclitaxel in the whole therapeutic strategy for ovarian cancer.

Cisplatin-associated anaemia in patients with solid tumours. A retrospective evaluation and considerations relative to erythropoietin administration.

We have reviewed the incidence of cisplatin-induced anaemia in patients affected with solid tumours treated with at least three courses of first-line cisplatin-containing regimens. In our experience, a low percentage (5%) of patients required transfusions of red blood cells. We think it is of the utmost importance to adopt uniform criteria in monitoring and treatment of patients at risk of developing cisplatin anaemia and to identify subsets of patients to eventually treat with erythropoietin.

Subcutaneous administration of interleukin 2 and interferon-alpha-2b in advanced renal cell carcinoma: a confirmatory study.

Recent clinical studies have suggested that the combination of subcutaneous recombinant human interleukin 2 (rIL-2) and interferon alpha (rIFN-alpha) is especially promising in advanced renal cell carcinoma. We assessed the safety, activity and toxicity of home therapy with these two agents in 50 patients. Each treatment cycle consisted of a 2 day pulse phase, with 9 x 10(6) IU m-2 of rIL-2 being given subcutaneously every 12 h, followed by a 6 week maintenance phase during which rIL-2 1.8 x 10(6) IU m-2 was administered subcutaneously every 12 h on days 1-5 and rIFN-alpha 2b 5 x 10(6) IU m-2 once a day on days 1, 3 and 5. Objective responses (CR+PR) occurred in 9/50 (18%) patients, six of whom (12%) achieved a complete response. Disease stabilisation was observed in 17 cases (34%) and 18 patients progressed during therapy. In the other six cases, treatment was interrupted early for toxicity or patient refusal. One patient died of myocardial infarction during the second cycle. The overall median survival was 12 months. Home therapy with subcutaneous rIL-2 + rIFN-alpha 2b proved to be active, feasible and moderately toxic, but serious adverse events can sometimes occur.

Cisplatinum based chemotherapy: role of the antiserotoninergic ondansetron in prevention of emesis.

Serotonin is a neurotransmitter involved in chemotherapy-induced emesis and ondansetron is a new drug endowed with selective antagonism against the 5HT3 receptors. Phase I-II studies have demonstrated its activity against acute emesis after single-dose cisplatin, reporting particularly low toxicity; in comparative studies with high-dose metoclopramide, it has been proved to be more effective and completely devoid of extrapyramidal side effects. Ondansetron has shown its activity and safety also in multiple-day cisplatin regimens. Its antiemetic efficacy is improved by the addition of dexamethasone. Preliminary data suggest its role also when used in single-dose administration. Its activity in the delayed phase of cisplatin emesis needs to be further explored.

A cisplatinum-cyclophosphamide regimen in advanced ovarian cancer: reporting 5-year results.

The following paper reports the evaluation of 53 consecutive patients with advanced ovarian epithelial carcinoma (FIGO stage III-IV), treated between October 1984 and December 1987 with immediate or delayed cytoreduction surgery and chemotherapy. Combination chemotherapy consisted of cisplatinum 45 mg/m2 i.v. for 2 consecutive days and cyclophosphamide 900 mg/m2 i.v. on the second day, administered every 28 days for a maximum of 8 courses. Objective responses were observed in 35 of 50 evaluable patients (70%), 17 (34%) of whom were pathological complete remissions (pCR). For patients with minimal residual disease before chemotherapy a higher pCR rate was achieved (10/20 vs. 7/30; p = N.S.). Median survival time of all patients was 29 months; subjects with minimal residual disease and good performance status before treatment had higher survival (48 vs. 22 months-p < 0.05 and 29 vs. 9 months-p < 0.05, respectively). Median time to progression was 25 months. After a median follow-up of 60 months, 15 (28%) patients were alive, 14 of whom disease-free. Toxicity was moderate with a particularly low incidence of nephrotoxicity and no case of serious long-lasting neuropathy. These findings suggest that the described combination has an efficacy comparable to other CDDP-containing combinations, using 2, 3 or more drugs, with a low incidence of acute serious toxicities and of disabling delayed sequelae.

A phase II study of combination chemotherapy in advanced ovarian carcinoma with cisplatin and cyclophosphamide plus reduced glutathione as potential protective agent against cisplatin toxicity.

AIMS AND BACKGROUND: The clinical use of cisplatin (CDDP), one of the most active agents in advanced ovarian cancer, is limited by nephrotoxicity and cumulative neurotoxicity. In preclinical studies, reduced glutathione (GSH) demonstrated a protective action against CDDP nephrotoxicity. We treated 20 patients with advanced ovarian carcinoma, with polychemotherapy containing CDDP + GSH, to assess the protective action of GSH against CDDP nephrotoxicity. METHODS: Between January 1988 and December 1989, 20 patients, with advanced ovarian carcinoma (St. III-IV-FIGO), not pretreated received CDDP: 45 mg/m2 i.v., on day 1-2, + cyclophosphamide (CPA): 900 mg/m2 i.v. on day 2 + GSH 2500 mg i.v. in normal saline 100 ml (in 15 min), before CDDP, every 21-28 days. RESULTS: A pathologic complete response rate (PCR) of 55% (11/20) was observed (7/14 patients with bulky disease). Median survival was 26.5 months and 5 patients were still alive and disease free at 35 months. Toxicity was limited, without any case of nephrotoxicity. CONCLUSIONS: On the basis of our previous experience with the same regimen without GSH, this study suggests that also in the clinical setting, GSH has no negative interference on CDDP activity and that GSH might improve the therapeutic index of CDDP. However, our data need to be confirmed by large randomized clinical studies.