An analysis of chemotherapy dose and dose-intensity in small-cell lung cancer: lessons to be drawn.

BACKGROUND: The survival in untreated small-cell lung cancer (SCLC) is <3 months. Prognosis has improved with chemotherapy, but remains poor. One of the issues concerning current chemotherapy is whether there is any benefit of increasing chemotherapy dose or dose intensity (DI). DESIGN: In the present review, 20 randomised studies, published in the period 1980-2001, in which dose or DI of chemotherapy in SCLC were the only variables tested, are analysed. The studies were categorised as follows: (i) number of cycles (treatment duration); (ii) dose per cycle; (iii) interval between cycles (dose densification); and (iv) a combination of these variables. RESULTS: (i) With treatment duration reduced to three to six cycles, median survival time (MST) was 2 months shorter, most evident in patients showing a (complete) response to initial chemotherapy. (ii) An improved survival was observed in two out of five high-dose studies. (iii) Survival was increased by 0.6 to 6.2 months in all four densification studies. (iv) Survival was not improved in studies that used dose-escalation and/or -densification in combination with a reduced number of cycles. The sample sizes were too small to be conclusive in most of the individual trials. The median of the MSTs in the 20 trials taken together was 9.8 months for the standard arms and 11.5 months for the intensified arms (i.e. more cycles, higher dose per cycle and/or shorter intervals). After omitting the two trials with reduced number of cycles in the so-called 'high-dose' arm, the median of MSTs was 8.7 and 11.5 months, respectively. There was only a slight improvement (1%) in 2-year survival for all trials taken together. However, when only taking high-dose and dose-densified chemotherapy trials into account, the difference in median 2-year survival became 19% (12% versus 31%). CONCLUSIONS: The above classification facilitates our understanding about doses of chemotherapy and it makes us appreciate the relevance of the individual determinants. It appears that the number of cycles, dose level, dose density, cumulative dose and DI are all important factors for improving survival. Intensification of chemotherapy still deserves further research in SCLC.

Vinorelbine and cisplatin in metastatic squamous cell carcinoma of the oesophagus: response, toxicity, quality of life and survival.

BACKGROUND: Vinorelbine and cisplatin are active against squamous cell oesophageal carcinoma. The purpose of this phase II study was to evaluate the efficacy and safety of vinorelbine plus cisplatin in previously untreated patients with metastatic squamous cell oesophageal carcinoma and to estimate the progression-free survival, overall survival and quality of life (QoL) of the patient population. PATIENTS AND METHODS: Seventy-one eligible patients were entered into a study of vinorelbine 25 mg/m2 on days 1 and 8 plus cisplatin 80 mg/m2 on day 1, every 3 weeks. Degree of dysphagia relief was monitored and QoL was measured using the EORTC QLQ-C30. RESULTS: All eligible patients were assessed for response and 24 achieved a confirmed partial response (33.8%; 95% confidence interval 23-46); the median duration of response was 6.8 months, progression-free survival was 3.6 months and median survival of the whole group was 6.8 months. Toxicity was mainly related to neutropenia (grade 3/4 in 41% of patients). At cycle 2, 43% of the patients reported at least a moderate improvement in global health status/QoL and 25% experienced a large improvement. CONCLUSIONS: Vinorelbine plus cisplatin represents a well-tolerated active palliative regimen for patients with advanced squamous cell carcinoma of the oesophagus. This combination may offer a better therapeutic index than cisplatin-5-fluorouracil.

Results of a randomised phase II study of cisplatin plus 5-fluorouracil versus cisplatin plus 5-fluorouracil with alpha-interferon in metastatic pancreatic cancer: an EORTC gastrointestinal tract cancer group trial.

A randomised phase II study of 5-fluorouracil (5-FU) plus cisplatin (CDDP) with or without alpha-interferon 2b was performed in patients with pancreatic cancer with measurable metastatic disease outside the pancreas. The treatment in arm A consisted of cisplatin (100 mg/m(2)) on day 1, followed by a continuous infusion of 5-FU 1000 mg/m(2) for 4 days and in arm B the same treatment was given plus alpha-interferon 2b in a dose of 3 million Units/day subcutaneously (s.c.) from day 1 for 5 days. 36 patients were entered in the trial, 18 in each arm. In arm B only 15 patients were eligible. No responses were observed in the 5-FU/CDDP arm and only 2 partial responses were achieved in the interferon-arm, lasting 27 and 32 weeks, respectively. Both treatment arms showed considerable toxicity. It has to be concluded that both treatment regimens have little activity and cannot be recommended.