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Biomedical subjects

D Maraninchi

Publications and source records attributed to D Maraninchi.

261 records · Page 15Linked to original sources
PubMedDate not supplied

Outpatient sequential high dose alkylation with stem cell support for patients with advanced breast cancer: a phase I-II study.

We evaluated the feasibility of administering, in an out-patient setting, a sequential high dose alkylating regimen with hematopoietic growth factor (HGF) and stem cell support to patients with advanced breast cancer. Peripheral blood stem cells (PBSC) were previously collected after chemotherapy and HGF. Two consecutive cycles of alkylating agents were planned: Thiotepa (T) then, 15 days later, BCNU (B). Three dose levels of each agent were administered in cohorts of consecutive patients: 400, 500 and 600 mg/m2 respectively. HGF and reinfusion of PBSC followed both cycles. Toxicity and response were evaluated according to the WHO recommendations. From April 1996 to August 1988, 30 women were enrolled: 8 in the first, 12 in the second and 10 in the third dose level. In all cases, B was administered after T with a median delay of 25 days because of grade 3/4 hematological toxicity. 4 patients did not receive B because of previous lung radiotherapy, persistent tricytopenia or insufficient PBSC collection. 19 patients with measurable lesions were considered for response. The objective response rate was 48% (11% CR, 37% PR). We recommended T and B at a dose of 600 mg/m2 to conduct a phase II study in metastatic breast cancer and even to administer B before T.

Antineoplastic Agents, Alkylating↗
PubMedDate not supplied

Pilot study of immunotherapy with interleukin-2 after autologous stem cell transplantation in advanced breast cancers.

Median survival for advanced breast cancer does not exceed 2 years. Immunotherapy following Hihg Dose Chemotherapy (HDC) and autologous stem cell transplantation (ASCT) is a procedure that could hypothetically decrease relapse rate. The mechanism implicated is induction of immune modulation and a possible Graft Versus Tumor effect (GVHT). Tolerance and feasibility of rIL-2 administered after HDC with ASCT was analyzed in twenty one advanced breast cancer patients. The patients were treated either with intra-venous high-dose rIL-2 (9 patients) or subcutaneous low dose (12 patients). With intra-venous high-dose rIL-2, 50% of the scheduled dose was administered and 100% of the scheduled dose was administered at a lower dose in the subcutaneous route. rIL-2 was administered safely after HDC and ASCT, particularly in the subcutaneous low dose arm. However no clinical beneficial effect was documented for these advanced heavily pretreated breast cancers. Immune modulation with rIL-2 earlier requires further investigation.

Adult↗
PubMedDate not supplied

Phase II study of a combination of cisplatin, all-trans-retinoic acid and interferon-alpha in squamous cell carcinoma: clinical results and pharmacokinetics.

UNLABELLED: Preclinical and clinical data suggest a certain antitumor efficacy for combination of retinoids, cytokines and cytotoxic compounds. PATIENTS AND METHODS: Between November 1994 and October 1996, 38 patients with advanced squamous cell carcinoma were enrolled in a phase II study to investigate an association of low-dose all-trans-retinoic acid (tRA) (40 mg/m2/day, 84 days), interferon-alpha (IFN-alpha) (6.10(6) UI/day, 84 days s.c.) and cisplatin (40 mg/m2/day, day 1, 28 and 56, i.v.). A Pharmacokinetic evaluation was performed on 12 patients. RESULTS: The incidence of grade 3/4 hematologic toxicities was moderate (< 20%). Extra hematological toxicities were frequent but easily manageable and not life threatening. However, treatment delivery was poor since only 6 patients (16%) received full therapy. Seven objective responses were observed (21%), suggesting some degree of synergism between tRA, IFN-alpha and cisplatin. Interestingly, continuous tRA treatment in combination with IFN-alpha and cisplatin did not induce a significant decrease in plasma levels, as had been previously described. CONCLUSIONS: Regarding the short median response duration and the frequency of toxic events, this regimen should no longer be recommended in pretreated patients with advanced disease. However, the consistent response rate reported here may warrant further investigation in an early setting.

Adult↗
PubMedDate not supplied

Phase I study of pegylated liposomal doxorubicin (Caelyx) in combination with carboplatin in patients with advanced solid tumors.

PURPOSE: To determine the maximum tolerated dose of the combination of Carboplatin and Caelyx, a pegylated liposomal doxorubicin, with promising activities in various solid tumors. PATIENTS AND METHODS: Twenty-two patients with various advanced solid tumors were included. Three dose levels of Caelyx were explored: 30, 35 and 40 mg/m2 in association with a fixed dose of Carboplatin (AUC 5) every 3 weeks. Dose escalation followed a modified continuous reassessment method. RESULTS: Dose-limiting toxicities were almost exclusively hematological: 3 febrile neutropenia, 1 grade 4 neutropenia lasting more than 7 days and 2 grade 4 thrombopenia were observed. Grade 4 neutropenia and febrile neutropenia were observed in 20 and 10% of courses, respectively. The median interval between courses was 25 days after cycle 1 and 27-28 days after subsequent cycles. Palmar-plantar erythrodysesthesia, mucositis and other non hematological toxicities were mild and uncommon. One patient experienced a severe anaphylactic reaction immediately after Caelyx infusion. No clinical heart dysfunction was observed. Three patients responded to therapy including 2 clinical complete responses in relapsing ovarian cancer. CONCLUSION: The recommended dose for future studies is Caelyx 35 mg/m2 + Carboplatin AUC 5 every 3 or 4 weeks. Antitumor activity, especially in ovarian cancer, warrants further investigation in phase II studies.

Adult↗
PubMedDate not supplied

High-dose alkylating agents with autologous hematopoietic stem cell support and trastuzumab in ERBB2 overexpressing metastatic breast cancer: a feasibility study.

BACKGROUND: ERBB2 overexpression predicts a worse outcome for patients receiving high-dose chemotherapy (HDC). Trastuzumab improves response rate and survival in ERBB2 overexpressing metastatic breast cancer patients (MBC). We investigated the feasibility of combining high-dose alkylating agents with autologous hematopoietic stem cell (AHSC) support and trastuzumab in ERBB2 overexpressing MBC. PATIENTS AND METHODS: Eleven consecutive patients with pre-treated ERBB2 overexpressing MBC were enrolled. HDC regimen consisted of a single course of cyclophosphamide 120 mg/kg + melphalan 140 mg/m2 (CyMEL, n =8), a single course of Thiotepa 600 mg/m2 (TTP, n = 1) or a sequential combination of Thiotepa 600 mg/m2 followed on day 21 by BCNU 600 mg/m2 (TTP-BCNU, n =2). Trastuzumab (4mg/kg) was started 24 h after AHSC infusion and then administered weekly (2 mg/kg). RESULTS: Median time to neutrophil and platelet recovery was 10 and 14.5 days, respectively. Three patients experienced febrile neutropenia and in 2 Herpes virus infections were documented. Five grade III/IV mucositis/oesophagitis were recorded. One patient experienced a reversible atrial arrhythmia on day 2 of trastuzumab, and another patients had a nonsymptomatic decrease in LVEF >10% on week 12 of trastuzumab. No toxic death was recorded. Median time to progression was 5 months (1 to 38 +). CONCLUSION: Combining alkylating agent-based HDC and trastuzumab appears to be feasible in ERBB2 overexpressing MBC and warrants further investigation in a larger cohort.

Adult↗
PubMedDate not supplied

[The role of autografts in severe or metastatic breast cancers].

Intensive treatment of poor prognosis breast cancer has included bone marrow autografts. A multicentric study was conducted from 1988 to 1992, including 105 patients with a minimal follow-up of 2 years after the autograft. Inclusion criteria were: age < 55 years, measurable metastasis, inflammatory breast cancer, breast cancer with major lymph node invasion (> 8 N+). Chemotherapy (6 to 8 cycles) was used initially. In responders, bone marrow was harvested and frozen. Medullary invasion had to be absent for bone marrow harvesting. Management then included cyclophosphamide: 60 mg/kg, D-7, D-6; mitoxantrone: 12 mg/m2, D-9 to D-5; alkeran: 140 mg/m2, D-2 followed D0 for bone marrow autograft. For the 105 patients, mean age was 40 years; inflammatory breast cancer: 33 patients; > or = 8 N+: 11 patients; metastasis: 61 patients. For the cases with metastasis, the main sites were: liver: 24 patients, lung: 14 patients, bone: 22 patients, central nervous system: 4 patients. Nineteen patients had at least two metastasis localizations. Responders alone were included although 7 patients had been stabilized before the autograft. For the metastatic forms, median survival was 41 +/- 9 months from the onset to diagnosis of metastasis, with 8 patients surviving over 5 years. Median survival without progression was 12 months with a 4-year probability of 17%. For inflammatory breast cancers, the probability of survival was 50% and survival without progression was 42%. For patients with lymph node invasion > or = 8 N+, it was 72%.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

rIL-2 in metastatic soft tissue sarcomas refractory to chemotherapy: response and enhancement of further chemosensitivity.

Chemotherapy (CT) in advanced and metastatic soft tissue sarcoma (STS) has a reported response rate of 17 to 30%, with a median survival of 30 months. Experimental and clinical studies have demonstrated some response with high-dose intravenous recombinant Interleukin-2 (r-IL2). We report a retrospective analysis of twelve patients with metastatic or locally evolutive STS who received high-dose rIL-2 immunotherapy: all patients were pre-treated with CT and were non responsive. All of these patients developed usual severe toxicity. One patient achieved a partial response with rIL-2 with more than 75% regression of lung metastases. All patients received CT post rIL-2 and 2 of them achieved a further response: 1 of them had a complete response (CR), and one had a partial response (PR). These results suggest that rIL-2 has a relatively low efficacy in patients with STS but that some of these patients can be, after rIL-2, responders to CT despite previous resistance.

Adult↗