Phase II study of vinorelbine in patients with androgen-independent prostate cancer.

PURPOSE: To evaluate the efficacy and toxicity of vinorelbine in a phase II study in patients with progressive metastatic androgen-independent prostate cancer. PATIENTS AND METHODS: Forty-seven men with progressive metastatic prostate cancer refractory to first-line or second-line hormonal therapy were treated with vinorelbine, a semisynthetic vinca-alkaloid. Vinorelbine was given, on an outpatient schedule, at 25 mg/m2 weekly for at least eight weeks or until progression or excessive toxicity. RESULTS: Forty-seven patients were included in the study, 33 being evaluable for tumour response, 36 for response to PSA, 21 for clinical benefit and 45 for toxicity. Median actual weekly dose was 19 mg/m2 (range 12.0-26.2 mg/m2). Six of thirty-six patients (17%) demonstrated a biologic response with a 50% or more decline in serum PSA on two consecutive measurements taken at least two weeks apart. The median duration of biologic response was 2.7 months. Two of three patients with measurable disease obtained an objective response but remained unconfirmed. No change disease was reported in 23 patients (49%). On entry into the study, 30 patients had symptomatic bone pain and required narcotic or non-narcotic analgesics. Clinical benefit from vinorelbine was achieved in 15 patients out of 21 (32% of the intent to treat analysis population and 71% of the assessable patients). Due to the low number of questionnaires (QLQ-C30) filled in, it was insufficient to allow any statistical analysis. The median survival was 10.2 months. Toxicity was mainly haematologic with 51% of patients experiencing grade 3 or 4 granulocytopenia. Three patients developed deep vein thrombosis. Non-haematologic toxicity, mainly nausea and neurotoxicity, was mild. CONCLUSION: The administration of weekly vinorelbine appears to be a safe treatment for those patients with androgen-independent prostate cancer and poor prognosis features who require chemotherapy. These results provide data for future investigation of vinorelbine in combination regimens.

Granulocyte-macrophage colony-stimulating factor in patients with neutropenic fever is potent after low-risk but not after high-risk neutropenic chemotherapy regimens: results of a randomized phase III trial.

PURPOSE: A randomized unblinded phase III trial was designed to determine the ability of granulocyte-macrophage colony-stimulating factor (GM-CSF) to accelerate recovery from febrile neutropenia induced by chemotherapy. PATIENTS AND METHODS: A total of 68 patients with febrile neutropenia following chemotherapy defined as axillary temperature greater than 38 degrees C and absolute neutrophil count (ANC) less than 1 x 10(9)/L were included. After stratification for high- and low-risk chemotherapy to induce febrile neutropenia, treatment was randomized between GM-CSF at 5 microg/kg/d or control, both being associated with antibiotics. RESULTS: GM-CSF significantly reduced the median duration of neutropenia from 6 to 3 days for ANC less than 1 x 10(9)/L(P < .001) and from 4 to 3 days for ANC less than 0.5 x 10(9)/L (P=.024), days of hospitalization required for febrile neutropenia, and duration of antibiotics during hospitalization. The greatest benefit with GM-CSF appeared for patients who had received low-risk chemotherapy, for which the median duration of ANC less than 1 x 10(9)/L was reduced from 7 to 2.5 days (P < .001) and from 4 to 2 days for ANC less than 0.5 x 10(9)/L (P=.0011), the duration of hospitalization during the study from 7 to 4 days (P=.003), and the duration on antibiotics during hospitalization from 7 to 3.5 days (P < .001). A multivariate analysis, using Cox regression, showed that variables predictive for recovery from neutropenia were GM-CSF (P=.0010) and time interval between the first day of chemotherapy and randomization (P=.030). There was no benefit for GM-CSF when high-risk chemotherapy was considered. CONCLUSION: GM-CSF significantly shortened duration of neutropenia, duration of neutropenic fever-related hospitalization, and duration on antibiotics during hospitalization when febrile neutropenia occurred after low-risk chemotherapy, but not high-risk chemotherapy.

[A phase II study with mitoxantrone-vinorelbine association in the treatment of advanced breast cancer in elderly women]. / Etude de phase II d'association mitoxantrone-vinorelbine dans le traitement du cancer du sein de la femme âgée.

To assess efficacy and toxicity of less toxic analogs for advanced breast cancer in elderly women, we performed a phase II study using the combination mitoxantrone (MTZ)-vinorelbine (VNR). From January 1991 to May 1993, 25 women older than 70 years received a chemotherapy consisting in 10 mg/m2 of MTZ on day 1, followed by 20 mg/m2 of VNR on day 1 and 8. Cycles were repeated every 21 days for a maximum of ten cycles in the case of an objective response. Sixteen women previously received first line hormonotherapy, eight with only one metastatic site. Twenty-three patients are evaluable for response and toxicity. An objective response was observed in five cases (22%), with a median time to progression of 13 months. More than 75% of the planned dose-intensity, for MTZ and VNR was received by 90 and 57.2% of patients, respectively. Dose-limiting toxicity was myelosuppression but no febrile neutropenia was observed. Extra haematologic toxicities were unfrequent. This combination is well tolerated by elderly women, but best results could be achieved by increasing delivered dose intensity.