A phase I dose escalation study of multicyclic, dose-intensive chemotherapy with peripheral blood stem cell support for small cell lung cancer
| Autor: | D Chou, Fumitake Gejyo, Kunihiko Sakai, Masaya Wakabayashi, T Shimbo, Hiroshi Tanaka, E Suzuki, Miho Takahashi, Kazuhisa Ito, Hiroshi Kagamu, Hirohisa Yoshizawa, Junta Tanaka, Masaaki Arakawa |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Adult
Male medicine.medical_specialty Lung Neoplasms Filgrastim Injections Subcutaneous medicine.medical_treatment Urology Transplantation Autologous Carboplatin chemistry.chemical_compound Antineoplastic Combined Chemotherapy Protocols Granulocyte Colony-Stimulating Factor Humans Medicine Ifosfamide Leukapheresis Carcinoma Small Cell Infusions Intravenous Etoposide Aged Transplantation Chemotherapy Radiotherapy business.industry Hematopoietic Stem Cell Transplantation Hematology Middle Aged Combined Modality Therapy Recombinant Proteins Surgery Granulocyte colony-stimulating factor Regimen Treatment Outcome chemistry Toxicity Female business medicine.drug |
| Zdroj: | Bone Marrow Transplantation. 25:5-11 |
| ISSN: | 1476-5365 0268-3369 |
| DOI: | 10.1038/sj.bmt.1702088 |
| Popis: | A phase I dose-escalation study of multicyclic, ifosfamide, carboplatin, and etoposide (ICE) with sequential reinfusion of peripheral blood stem cells (PBSCs) was conducted to determine the maximum-tolerated dose (MTD) of ICE. Twenty-four patients with SCLC (LD: 6, ED: 18) were treated with ifosfamide (3000-9000 mg/m2, 24-h infusion), carboplatin (300-400 mg/m2), and etoposide (300 mg/m2) followed by subcutaneous filgrastim (75 microg/day) from day 4 to the day of PBSC collection. PBSC were harvested when the WBC count reached/=5 x 109/l. The leukapheresis product was cryopreserved and reinfused on day 4 of the next cycle, which was started 48 h after the last PBSC collection. The ifosfamide dose was escalated as follows: 3000 mg/m2 (level 1), 5000 mg/m2 (level 2), 7000 mg/m2 (level 3), 9000 mg/m2 (level 4). Patients with LD were treated with concurrent radiotherapy at 1.5 Gy twice daily for the initial 3 weeks to a total dose of 45 Gy and MTD, defined separately. Patients were evaluated for hematologic and non-hematologic toxicity, actual dose intensities, as well as response to therapy. The maximum-tolerated dose (MTD) was defined as the dose level at which more than 5 days of grade 4 myelo- suppression or non-hematologic toxicity greater than grade 3 developed in two thirds of the patients. For ED cases, MTD was level 4 and the recommended dose of ifosfamide was 7000 mg/m2. For LD cases, the recommended dose of ifosfamide was 5000 mg/m2. The dose limiting toxicity of multicyclic ICE was hemato- logic toxicity and CNS toxicity which manifested as ataxia. Tumor responses were seen in all patients, with 14 patients showing a complete response. The actual total dose-intensity at the recommended dose level was 2.2 and 1.74, for ED and LD, respectively, compared with previously reported ICE regimens. PBSC support for dose-intensive ICE regimen permitted dose escalation of ifosfamide with a mean interval of 16-17 days. We conclude that this regimen is well tolerated, with acceptable hematological and non-hematological toxicity. Bone Marrow Transplantation (2000) 25, 5-11. |
| Databáze: | OpenAIRE |
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