Dose escalation of CPT-11 in combination with oxaliplatin using an every two weeks schedule: a phase I study in advanced gastrointestinal cancer patients.

Abstract

BACKGROUND:

To determine the dose-limiting toxicity of CPT-11 in combination with oxaliplatin, and the maximal tolerated dose (MTD) and the recommended dose (RD) of CPT-11 using an every two weeks schedule.

PATIENTS AND METHODS:

The study was designed to evaluate escalated doses of CPT-11 starting at 100 mg/m2 with a fixed clinically-relevant dose of 85 mg/m2 oxaliplatin given every two weeks.

RESULTS:

Twenty-three patients and 186 cycles were evaluable for toxicity (median per patient: 7, range: 1-13). Grade 3 oxaliplatin-induced neurotoxicity was cumulative and limiting in 39% (9 of 23) of patients. The MTD of CPT-11 was 200 mg/m2, with incomplete neutrophil recovery at day 15 as limiting toxicity. At the RD (175 mg/m2 of CPT-11): no grade 4 neutropenia was seen in the two first cycles; 30% of patients experienced grade 3-4 diarrhea. Febrile neutropenia (3.2% of all cycles) was 3-fold more frequent in performance status (PS) 2 than in PS0-1 patients. Among eleven colorectal cancer (CRC) patients, three complete and four partial responses were documented, including in three 5-fluorouracil (5-FU) refractory patients.

CONCLUSION:

To combine CPT-11 175 mg/m2 and oxaliplatin 85 mg/m2 every two weeks is feasible in an outpatient setting, and very active in 5-FU resistant CRC patients. A dose of 150 mg/m2 CPT-11 is recommended in PS2 patients.

• Authors: F Goldwasser, M Gross-Goupil, J M Tigaud, M Di Palma, J Marceau-Suissa, E Wasserman, A Yovine, J L Misset, E Cvitkovic
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 11 Issue 11 Pg. 1463-70 (Nov 2000) ISSN: 0923-7534 [Print] England
• PMID: 11142487 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antimetabolites, Antineoplastic
• Organoplatinum Compounds
• Oxaliplatin
• Irinotecan
• Fluorouracil
• Camptothecin

Topics

• Adult
• Aged
• Alopecia (chemically induced)
• Antimetabolites, Antineoplastic (pharmacology)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects, therapeutic use)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
• Diarrhea (chemically induced)
• Drug Administration Schedule
• Drug Resistance, Neoplasm
• Esophageal Neoplasms (drug therapy, mortality, pathology)
• Female
• Fluorouracil (pharmacology)
• Gastrointestinal Neoplasms (drug therapy, mortality, pathology)
• Hematologic Diseases (chemically induced)
• Humans
• Infections (chemically induced)
• Irinotecan
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Metastasis
• Neutropenia (chemically induced)
• Organoplatinum Compounds (administration & dosage, adverse effects)
• Oxaliplatin
• Salvage Therapy
• Sensation Disorders (chemically induced)
• Treatment Outcome