High activity and reduced neurotoxicity of bi-fractionated oxaliplatin plus 5-fluorouracil/leucovorin for elderly patients with advanced colorectal cancer.

BACKGROUND: The proportion of elderly within the general population is increasing and the incidence of colorectal cancer increases with age. Oxaliplatin and 5-fluorouracil (FU) combination is active in this disease. PATIENTS AND METHODS: This multicenter phase II study was designed to investigate feasibility, efficacy, activity of daily living (ADL) and instrumental activity of daily living (IADL) in elderly patients with metastatic colorectal cancer treated, as first-line chemotherapy, with a bi-fractionated oxaliplatin/5-FU based regimen. Treatment was oxaliplatin 45 mg/m2, leucovorin 200 mg/m2, 5-FU 400 mg/m2 and 22 h continuous infusion of 5-FU 600 mg/m2, all given intravenously on days 1 and 2, every 2 weeks. RESULTS: Seventy-eight patients were enrolled; median age was 75 years (range 70-85). Among 77 evaluable patients, we observed seven complete responses and 32 partial responses, for an overall response rate of 51% (95% confidence interval 40% to 62%). A stabilization of disease was observed in 25% of patients while 19 patients progressed. Canadian NCI grade 3/4 toxicities were: neutropenia in 32% of patients (febrile in two), diarrhea in 10%, mucositis in 4%, and fatigue in 4%. Sensory neuropathy was mild and occurred as grade 3 in 6% of patients. ADL and IADL scores did not change significantly during treatment. CONCLUSIONS: The bi-fractionated delivery of oxaliplatin plus 5-FU/leucovorin demonstrated high antitumor activity in elderly patients with advanced colorectal cancer. Splitting oxaliplatin administration might reduce incidence of severe neuropathy, although this has to be confirmed by further studies.

Long-survival in responding patients with metastatic breast cancer treated with doxorubicin-docetaxel combination. A multicentre phase II trial.

BACKGROUND: The doxorubicin-docetaxel combination is active in breast cancer; the aim of the present study was to evaluate the complete response rate and safety profile of the doxorubicin and docetaxel regimen as first-line chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS: Forty-three patients entered the study. Treatment plan was: doxorubicin (50 mg/m2, i.v. bolus) followed 1 hour later by docetaxel (75 mg/m2 i.v. infusion over 1 hour), q 3 weeks, for up to six courses. The patients achieving a response or a stabilisation of disease after 6 courses were allowed to intensify the treatment with docetaxel (100 mg/m2, q 3 weeks) for up to 2 courses. G-CSF (or GM-CSF) was administered if clinically indicated. RESULTS: Patients' median age was 57years (range 32-75) and 72% of them had visceral disease. A total of 217 doxorubicin-docetaxel courses were delivered, with 70% of patients receiving all the 6 planned cycles. Among the 40 patients assessable for response (WHO criteria), 7 (16%) achieved a complete remission and 22 (51%) a partial remission, for an overall response rate (intent-to-treat) of 67% (95% C.I. =53% to 81%). In 19 patients, the treatment was intensified with two more single-agent docetaxel cycles, without ameliorating the response. Twenty-seven patients with oestrogen receptor-positive received hormonal therapy as 'maintenance' after completing chemotherapy treatment. NCIC G3-G4 neutropenia was recorded in 58% of patients, with G/GM-CSF used in 23 (53%) patients and 91 (38%) cycles. No patients experienced severe cardiac or neurological toxicity. No toxic death occurred. With a median follow-up of 41 months among alive patients, we observed in responder patients an overall median time to progression and survival of 18 and 33 months respectively, with ten long-survivors still alive. CONCLUSION: This study confirmed the combination doxorubicin-docetaxel as a very active regimen for metastatic breast cancer. Remarkably long survival times were observed not only in complete responders, but also in those patients who responded partially. This might be equally attributed to first-line treatment and sequential maintenance hormonal therapy.