Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study.

BACKGROUND: Docetaxel/cisplatin/infusional 5-fluorouracil (5-FU; DCF) is a standard chemotherapy regimen for patients with advanced gastric cancer (GC). This phase II study evaluated docetaxel/oxaliplatin (TE), docetaxel/oxaliplatin/5-FU (TEF), and docetaxel/oxaliplatin/capecitabine (TEX) in patients with advanced GC. PATIENTS AND METHODS: Patients with metastatic or locally recurrent gastric adenocarcinoma (including carcinoma of the gastro-oesophageal junction) were randomly assigned (1 : 1 : 1) to TE, TEF, or TEX. Each regimen was tested at two doses before full evaluation at optimized dose levels. The primary end point was progression-free survival (PFS). Overall survival (OS), tumour response, and safety were also assessed. A therapeutic index (median PFS relative to the incidence of febrile neutropenia) was calculated for each regimen and compared with DCF (historical data). RESULTS: Overall, 248 patients were randomly assigned to receive optimized dose treatment. Median PFS was longer with TEF (7.66 [95% confidence interval (CI): 6.97-9.40] months) versus TE (4.50 [3.68-5.32] months) and TEX (5.55 [4.30-6.37] months). Median OS was 14.59 (95% CI: 11.70-21.78) months for TEF versus 8.97 (7.79-10.87) months for TE and 11.30 (8.08-14.03) months for TEX. The rate of tumour response (complete or partial) was 46.6% (95% CI 35.9-57.5) for TEF versus 23.1% (14.3-34.0) for TE and 25.6% (16.6-36.4) for TEX. The frequency and type of adverse events (AEs) were similar across the three arms. Common grade 3/4 AEs were fatigue (21%), sensory neuropathy (14%), and diarrhoea (13%). Febrile neutropenia was reported in 2% (TEF), 14% (TE), and 9% (TEX) of patients. The therapeutic index was improved with TEF versus TEX, TE, or DCF. CONCLUSION: These results suggest that TEF is worthy of evaluation as an arm in a phase III trial or as a backbone regimen for new targeted agents in advanced GC. CLINICALTRIALS.GOV: Identifier Trial registration number: NCT00382720.

Randomized phase II study of docetaxel plus estramustine and single-agent docetaxel in patients with metastatic hormone-refractory prostate cancer.

BACKGROUND: Docetaxel (Taxotere)-based regimens are the new standard therapy in advanced hormone-refractory prostate cancer (HRPC). A synergistic activity has been shown with docetaxel in combination with estramustine in vitro; however, the benefit of this combination remains controversial in clinical practice. We assessed the activity and safety of docetaxel alone and docetaxel-estramustine in HRPC. PATIENTS AND METHODS: Patients (n = 92) with metastatic HRPC and rising prostate-specific antigen (PSA) while receiving androgen suppression were randomized to 3-weekly treatment with either docetaxel 75 mg/m(2), day 1 (D), or docetaxel 70 mg/m(2), day 2, plus oral estramustine 280 mg twice daily, days 1-5 (DE). RESULTS: Ninety-one patients were treated (DE 47, D 44). A PSA response occurred in 68% (primary endpoint met) and 30% of patients, respectively. Median PSA response duration was 6.0 months in both groups. Median time to progression was 5.7 and 2.9 months, and median survival was 19.3 and 17.8 months in the DE and D arms, respectively. Hematologic and non-hematologic toxic effects were mild and similar in both arms. One patient in each group withdrew due to toxicity. Quality of life was similar in both groups. CONCLUSION: Combining estramustine with docetaxel in this schedule is an active and well-tolerated treatment option in HRPC.

[Management of non-small cell lung carcinoma following docetaxel-cisplatin. Results of an epidemiologic survey]. / Prise en charge des cancers bronchiques non à petites cellules après docétaxel-cisplatine. Résultats d'une étude observationnelle.

BACKGROUND: The purpose of this epidemiologic survey was to describe the management of second-line therapy for patients with stage IIIB-IV non-small cell lung carcinoma (NSCLC) following docetaxel-cisplatin as first-line therapy. METHODS: Between June 2003 and December 2004, 265 patients were enrolled. The data registered were the choice of cytotoxics, the safety profile, the efficacy and the clinical benefit. RESULTS: Two hundred and sixty one patients were treated with docetaxel-cisplatin as a first-line regimen and 181 received a second line. This second line was a single agent regimen in 58% of cases and a gemcitabine based treatment in 60.8%. The main criterion for the choice of second-line therapy was the safety profile in 34.3% of cases. The overall response rate was 16.6% after the second line and clinical benefit was reported in 43.6% of patients. CONCLUSION: In more than 2/3 of patients with NSCLC the docetaxel-cisplatin combination leaves the opportunity to give a second-line treatment, providing satisfying results in terms of clinical benefit. In this study gemcitabine was the most widely prescribed second-line treatment, mainly as a single agent.

Dose-escalation study of single dose mitoxantrone in combination with timed sequential chemotherapy in patients with refractory or relapsing acute myelogenous leukemia.

A dose-escalation study was realized in order to assess the maximally tolerated dose (MTD) of high-dose mitoxantrone in a single injection combined with cytarabine and etoposide (EMA regimen) in refractory or relapsed acute myelogenous leukemia (AML). Between July 1997 and June 1998, 24 patients with relapsed or refractory AML entered the study. All but one patient had normal left ventricular ejection fraction (LVEF) at baseline. Performance status according to World Health Organization (WHO) criteria was less than two in all cases. All patients have been previously treated by mitoxantrone or anthracyclines. Four cohort of ten patients were scheduled with the following doses: (1) mitoxantrone 36 mg/m2 on day 1; (2) mitoxantrone 45 mg/m2 on day 1; (3) mitoxantrone 60 mg/m2 on day 1; (4) mitoxantrone 75 mg/m2 on day 1 in combination with cytarabine 500 mg/m2 per day (days 1-3, and days 8-10), and etoposide 200 mg/m2 per day (days 8-10). All patients received the full doses of the three drugs. The limiting toxicity was defined as WHO grade 4 nonhematologic toxicity and for impairment of cardiac function by Alexander's criteria (moderate or severe toxicity). The occurrence of limiting toxicity in at least three patients from the same dose level determined the MDT. No limiting toxicity was observed in mitoxantrone dose level 1. Two limiting toxicities were observed in mitoxantrone dose level 2 (one mucositis, one moderate cardiac toxicity), and three limiting toxicities in mitoxantrone dose level 3 (1 high transaminase levels, two moderate cardiac toxicities) ending the assay. Overall, 16 patients (67%) achieved complete remission (CR). One drug-addict patient died from cerebral hemorrhage due to severe aspergillosis and was not considered as a limiting toxicity. After EMA chemotherapy, 13 patients received subsequent chemotherapy courses involving anthracyclines or their derivatives. Six patients underwent allogeneic bone marrow transplantation. No late toxicity occurred. The median survival of the entire cohort was 41.4 weeks. We conclude that (i) EMA chemotherapy using a single injection of mitoxantrone is effective in the treatment of refractory or relapsing AML; (ii) the recommended phase II dose of mitoxantrone is 45 mg/m2 administered over 30 min as a single dose in combination with cytarabine and etoposide.