ABSTRACT
Topotecan has demonstrated activity in ovarian carcinomas. In order to increase the tumour response rate and to define the maximum tolerated dose (MTD) of topotecan, we decided to develop a high-dose phase I regimen supported by stem cell support. High-doses schedules using a 1-day single administration have MTDs of 10.5 (24 h continuous infusion (CI)) or 22.5 mg/m2 (30 min infusion). Five-day CI induces grade IV mucositis at high doses (MTD<12 mg/m2). We chose to administer topotecan in a 5-day schedule with a 30 min daily infusion. Patients were scheduled to receive one cycle of therapy. The first dose level was 4.0 mg/m2/day x 5 days. Limiting toxicities were defined as toxic death, grade IV non-haematopoietic or haematopoietic toxicity >6 weeks. From August 1998 to April 2002, 49 patients were included. Forty-three patients have completed one course and 15 have received two cycles. One patient treated at level 7 mg/m2/day died of sepsis. Median duration of grade IV neutropenia was 9 days. Two episodes of grade IV diarrhoea were observed at level 9.5 mg/m2/day. Pharmacokinetic data were linear within the dose range of 4-9.0 mg/m2/day. The MTD was reached at 9 mg/m2/day x 5 days.
Subject(s)
Carcinoma/drug therapy , Hematopoietic Stem Cell Transplantation , Ovarian Neoplasms/drug therapy , Topotecan/administration & dosage , Adolescent , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Combined Modality Therapy , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Hematopoietic Stem Cell Mobilization/adverse effects , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Maximum Tolerated Dose , Middle Aged , Survival Rate , Topotecan/adverse effects , Topotecan/pharmacokinetics , Treatment OutcomeABSTRACT
In endemic zones, the atovaquone-proguanil (AP) combination is well tolerated and effective in treating acute, uncomplicated malaria. Trials involving non-immune patients are lacking, however. We conducted a randomized, multicenter open-label trial to determine the efficacy and tolerability of the AP combination (1,000 mg + 400 mg once daily for 3 days) in comparison with halofantrine (HF) (1,500 mg in 3 doses) in non-immune adults with imported uncomplicated Plasmodium falciparum malaria. Follow-up visits were programmed on Days 7, 14, 21, 28, and 35 after hospital discharge. Out of 48 patients enrolled in the study, 41 were assessable for the cure rate (21 in the AP group and 20 in the HF group). All the patients were cured. The mean parasite clearance time was longer (63+/-23 hours) in the AP group than in the HF group (48+/-15 hours) (P = 0.02). The frequency of gastrointestinal adverse events was higher in the AP group. No noteworthy electrocardiographic changes were observed, particularly in the QTc interval. The AP combination appears to be a valuable alternative treatment in non-immune adults.
Subject(s)
Antimalarials/administration & dosage , Malaria, Falciparum/drug therapy , Naphthoquinones/administration & dosage , Phenanthrenes/administration & dosage , Proguanil/administration & dosage , Acute Disease , Administration, Oral , Adolescent , Adult , Atovaquone , Drug Therapy, Combination , Female , France , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
OBJECTIVE: To evaluate the efficacy and safety of liposomal encapsulated daunorubicin (DaunoXome) in the treatment of AIDS-associated mucocutaneous Kaposi's sarcoma. DESIGN: A Phase II, multicentre, European, non-comparative, open study to assess the use of DaunoXome in patients with no prior anthracycline chemotherapy for Kaposi's sarcoma. The response rate, time to disease progression, and the incidence and severity of adverse events were documented. SETTING: Hospital-based HIV units. PATIENTS: Thirty HIV-seropositive patients with mucocutaneous Kaposi's sarcoma were enrolled and treated. INTERVENTIONS: Treatment with DaunoXome at a dose of 40 mg/m2 intravenously once every 2 weeks. Treatment with antiretroviral agents and prophylaxis of opportunistic infections where indicated. RESULTS: Of the 30 evaluable patients, 22 patients (73%) achieved a partial response. Median time to treatment response was 30 days (range, 15-202). For patients with a partial response, median time to treatment failure was 153 days (range, 15-558). Patients received a median of 10 cycles (range, 1-44). Adverse events were minimal. The most common side effect was granulocytopenia in 16 patients (53%). CONCLUSION: DaunoXome is an effective and well-tolerated treatment for AIDS-associated mucocutaneous Kaposi's sarcoma and can be administered for prolonged periods. The myelosuppression can be managed by dose reductions and dose not preclude the concurrent use of antiretroviral therapies.
