A phase I study of larotaxel (XRP9881) administered in combination with carboplatin in chemotherapy-naïve patients with stage IIIB or stage IV non-small cell lung cancer.

Abstract

PURPOSE:

This primary objective of this phase I dose-escalation study was to define the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of larotaxel administered in combination with carboplatin in chemotherapy-naïve patients with advanced/metastatic non-small cell lung cancer (NSCLC).

METHODS:

Eighteen patients with stage IIIB or IV NSCLC, in cohorts of three to six evaluable patients, were to receive every 3 weeks: larotaxel beginning at 45 mg/m(2) administered as a 1-h infusion, followed after 30 min by carboplatin (area under the concentration-time curve (AUC) = 6 mg/mL × min, later AUC = 5) as a 1-h infusion. Dose escalation of larotaxel up to 90 mg/m(2) was permitted according to DLT occurrence. Patients received ondansetron as prophylactic anti-emetic premedication.

RESULTS:

In view of the toxicity encountered, the carboplatin dose was decreased for the later part of the study to AUC = 5 mg/mL × min. Eight of 18 treated patients experienced DLTs in the first cycle, including neutropenia and associated complications, diarrhea and fatigue. The MTD of the combination was defined as larotaxel 60 mg/m(2) with a carboplatin AUC of 6 mg/mL × min. Neutropenia, reported at grade 3/4 in 15/18 patients (83%), was the most common severe adverse event, reaching grade 4 in 14 patients (78%). Eleven patients (61%) experienced grade 3/4 non-hematological toxicity, predominantly dehydration, fatigue, infection, nausea and vomiting. One patient (6%) achieved a partial response and 11 (61%) had stable disease.

CONCLUSIONS:

The combination of larotaxel and carboplatin is feasible and shows modest activity in chemotherapy-naïve patients with advanced/metastatic NSCLC. The principal toxicity was grade 3/4 neutropenia.

• Authors: Francisco Robert, Karen Harper, Judie Ackerman, Sunil Gupta
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 65 Issue 2 Pg. 227-34 (Jan 2010) ISSN: 1432-0843 [Electronic] Germany
• PMID: 19479255 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Taxoids
• Carboplatin
• larotaxel

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Female
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Metastasis
• Neoplasm Staging
• Taxoids (administration & dosage)