A phase I/randomized phase II, non-comparative, multicenter, open label trial of CP-547,632 in combination with paclitaxel and carboplatin or paclitaxel and carboplatin alone as first-line treatment for advanced non-small cell lung cancer (NSCLC).

Abstract

PURPOSE:

To evaluate the toxicity profile and pharmacological properties of oral CP-547,632 alone and in combination with paclitaxel and carboplatin administered every 3 weeks, and to assess efficacy as measured by the objective response and progressive disease rates of oral CP-547,632 administered in combination with paclitaxel and carboplatin.

PATIENTS AND METHODS:

Patients with stage IIIB/IV or recurrent non-small cell lung cancer receiving first-line chemotherapy were treated with oral daily CP-547,632 in combination with paclitaxel 225 mg/m(2) and carboplatin AUC = 6 every 3 weeks. Pharmacokinetics parameters for CP-547,632 and paclitaxel were determined independently and during co-administration.

RESULTS:

Seventy patients were enrolled and 68 patients were treated, 37 in phase 1 and 31 in phase 2 (14 with the combination and 17 with chemotherapy alone). Dose-limiting toxicity of CP-547,632 250 mg by mouth daily in combination with paclitaxel and carboplatin was grade 3 rash and grade 3 diarrhea despite medical intervention. CP-547,632 did not significantly affect the pharmacologic profiles of paclitaxel and carboplatin. No subject had CR. In phase I, seven subjects (22.6%) had a confirmed partial response. In phase II, four subjects (28.6%) receiving CP-547,632 plus chemotherapy had a confirmed partial response. In the phase II chemotherapy alone group, four subjects (25%) had a confirmed partial response.

CONCLUSION:

The combination of CP-547,632 and paclitaxel and carboplatin was well-tolerated at doses up to 200 mg by mouth daily. Dose-limiting toxicity of CP-547,632 at 250 mg consisted of diarrhea and rash. CP-547,632 did not increase the objective response rate to chemotherapy alone in patients with advanced non-small cell lung cancer.

• Authors: Roger B Cohen, Corey J Langer, George Rajan Simon, Peter David Eisenberg, John Daniel Hainsworth, Stefan Madajewicz, Thomas Michael Cosgriff, Kristen Pierce, Huiping Xu, Katherine Liau, Diane Healey
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 60 Issue 1 Pg. 81-9 (Jun 2007) ISSN: 0344-5704 [Print] Germany
• PMID: 17031646 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• 3-(4-bromo-2,6-difluorobenzyloxy)-5-(3-(4-pyrrolidin-1-ylbutyl)ureido)isothiazole-4-carboxylic acid amide
• Thiazoles
• Urea
• Carboplatin
• Paclitaxel

Topics

• Administration, Oral
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, pharmacokinetics, therapeutic use)
• Area Under Curve
• Carboplatin (administration & dosage, adverse effects, pharmacokinetics)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Diarrhea (chemically induced)
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Exanthema (chemically induced)
• Female
• Gastrointestinal Diseases (chemically induced)
• Half-Life
• Hematologic Diseases (chemically induced)
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Middle Aged
• Neoplasm Staging
• Paclitaxel (administration & dosage, adverse effects, pharmacokinetics)
• Prognosis
• Thiazoles (administration & dosage, adverse effects, pharmacokinetics)
• Treatment Outcome
• Urea (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)