Induction docetaxel and carboplatin followed by weekly docetaxel and carboplatin with concurrent radiotherapy, then surgery in stage III non-small cell lung cancer: a Phase I study.

Abstract

PURPOSE:

To determine the maximum-tolerated dose of docetaxel (DOC) in combination with carboplatin (CAR) and thoracic radiotherapy (RT), in the setting of trimodality treatment of patients with stage III non-small cell lung cancer (NSCLC).

EXPERIMENTAL DESIGN:

Thirty-two patients with biopsy-proven stage IIIA (n = 20) or IIIB (n = 12) NSCLC were given two initial cycles of CAR (area under the curve = 6) and DOC (75 mg/m(2)), subsequent RT (54 Gy) with concurrent weekly CAR (area under the curve = 2), and DOC at six dose levels from 10 to 40 mg/m(2), then surgery if the patient's disease was resectable.

RESULTS:

Three patients did not complete induction computed tomography (CT). Twenty-nine patients received concurrent CT/RT. Fifteen patients were eligible for surgery. Dose-limiting toxicities occurred in 2 patients, at dose levels two (atrial fibrillation) and three (transaminitis). The maximum-tolerated dose, as defined by the protocol, was not reached, although grade 3 and 4 toxicities were encountered at all dose levels. The most common more than or equal to grades 3 toxicities were neutropenia, nausea, vomiting, and fatigue. Four patients (13.3%) responded to induction CT. Ten patients (38.5%) responded to CT/RT. Eight surgical patients (57.1%) were downstaged, including 3 pathologic complete responses. Median relapse free and overall survivals are 8.5 and 12 months. One-year and estimated 2-year survival rates are 56.3 and 34.3%.

CONCLUSION:

This new regimen for stage III NSCLC of induction CAR/DOC, then weekly CAR/DOC with concurrent RT followed by surgery, can be safely administered and offers encouraging results. DOC at 30 mg/m(2) in combination with CAR and RT is recommended for Phase II study.

• Authors: Lori J Wirth, Joan Lucca, Patricia Ostler, Panos Fidias, Cathy Lynch, Pasi A Jänne, Roy S Herbst, Bruce E Johnson, David J Sugarbaker, Douglas J Mathisen, Jeanne M Lukanich, Noah C Choi, Stuart M Berman, Arthur T Skarin
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 9 Issue 5 Pg. 1698-704 (May 2003) ISSN: 1078-0432 [Print] United States
• PMID: 12738723 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Taxoids
• Docetaxel
• Carboplatin

Topics

• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carboplatin (administration & dosage)
• Carcinoma, Non-Small-Cell Lung (drug therapy, radiotherapy, surgery, therapy)
• Combined Modality Therapy
• Docetaxel
• Dose-Response Relationship, Drug
• Female
• Humans
• Lung Neoplasms (drug therapy, radiotherapy, surgery, therapy)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasm Staging
• Remission Induction
• Taxoids (administration & dosage)
• Treatment Outcome