Escalating doses of carboplatin with high-dose ifosfamide using autologous bone marrow as support: a phase I study.

Abstract

In this phase I study, 16 adult cancer patients were treated with concurrent 4-day continuous infusions of ifosfamide at 12 g/m2 and escalating doses of carboplatin (400-1600 mg/m2) to determine the major non-haematological dose-limiting toxicity of the combination. Mesna was given by continuous infusion over 5 days for uroprotection (total dose per course = 15 g/m2). Autologous bone marrow support, which was mandated for subsequent dose levels once granulocytes remained below 500/microliters for more than 14 days in at least 2 patients entered at a given dose level, was used at dose levels above 400 mg/m2 carboplatin. Renal toxicity became dose-limiting at the maximum tolerated dose level of 1600 mg/m2 carboplatin. Temporary creatinine elevations above 2 mg/dl (median peak 2.6 mg/dl) were observed in 3 and irreversible renal toxicity occurred in 1 (peak creatinine 6.9 mg/dl, chronic creatinine 5-6 mg/dl) of the 5 patients entered at this dose level. Severe confusion and lethargy associated with rising creatinine developed in 2 patients. Two complete and four partial responses were documented in 14 heavily pretreated evaluable patients. The complete responses continue at 14+ and 20+ months in a patient with germ cell carcinoma and Ewing's sarcoma, respectively. Carboplatin appears to contribute to the renal toxicity of ifosfamide. Nevertheless, the combination of carboplatin and ifosfamide at 80% and 75% of the single-agent maximal tolerated doses respectively produced acceptable non-haematological toxicity. Further studies in the treatment of sarcoma, germ cell, ovarian and lung carcinomas with this combination are warranted.

• Authors: A D Elias, L J Ayash, J P Eder, C Wheeler, J Deary, L Weissman, M Hunt, J Critchlow, L Schnipper, E Frei 3rd
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 117 Suppl 4 Pg. S208-13 ( 1991) ISSN: 0171-5216 [Print] Germany
• PMID: 1795009 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carboplatin
• Ifosfamide

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Bone Marrow Transplantation
• Carboplatin (administration & dosage)
• Combined Modality Therapy
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Evaluation
• Humans
• Ifosfamide (administration & dosage)
• Neoplasms (drug therapy)
• Remission Induction
• Transplantation, Autologous