Docetaxel and carboplatin once every 3 weeks versus weekly docetaxel in advanced non-small cell lung cancer. Interim analysis of a multicenter phase III trial

Reviewer: S. Jack Wei, MD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 1, 2003

Presenter: H. Groen
Presenter's Affiliation: Dutch Chest Physicians Association
Type of Session: Scientific

Background

Taxane-based chemotherapy has been shown to have a modest response rate of 10-30% in advanced non-small cell lung cancer (NSCLC). Taxanes are often given in conjunction with platinum-based chemotherapy for these patients. Significant toxicity can result from the delivery of platinum-based drugs. A multi-instutional randomized phase III trial was conducted to compare a taxane/platinum combination regimen with a taxane alone regimen, given more frequently.

Materials and Methods

297 patients with stage IIIB/IV NSCLC were randomized and 229 completed treatment from June 2000 to October 2002 prior to interim analysis.
Eligibility criteria included stage IIIB or IV NSCLC, no previous chemotherapy, ECOG performance status 0-2, adequate organ function, and no symptomatic brain metastases.
Patients were randomized to 2 arms: 1) docetaxel (75 mg/m2) + carboplatin (AUC 6) given every 3 weeks for a total of 5 cylcles (DC arm) or 2)docetaxel (35 mg/m2) alone given weekly for 6 weeks, followed by a 2 week rest period, for a total of 3 cycles (Dw arm).
The two treatment arms were well balanced with regards to stage, age, performance status, and histologic subtype

Results

The study was closed early at interim analysis due to the superior performance for patients on the DC arm
Patients on the DC arm were more likely to complete all cycles of chemotherapy than patients in the Dw arm (59.4% vs. 14.5%). The most common reason for stopping treatment was progressive disease (PD).
PD occurred more frequently in the first 6 weeks of treatment in the Dw arm compared to the DC arm (33% vs. 8%).
Overall response rate was higher in the DC arm than the Dw arm (39% vs 16%, p<0.001)
Median survival was improved in the DC arm (40 wks vs. 27 wks, p=0.02) as was time to progression (22 wks vs. 10 wks, p<0.001).
Higher rates of leukopenia (35% vs. 5%) and febrile neutropenia (8% vs. 0%) were seen with the DC arm; however higher rates of nail and skin toxicities were seen in the Dw arm.
Quality of life analysis showed more fatigue and pain, and worse global health status and physical function in the Dw arm at 12 weeks.

Author's Conclusions

The DC arm showed superior median survival, time to progression, and quality of life compared to the Dw arm.
Higher rates of progressive disease, especially early in the treatement course, was seen in the Dw arm.
The DC arm was somewhat more toxic than the Dw arm, particularly with regards to hematologic toxicities; however patients in the DC arm had less skin and nail toxicities than patients in the Dw arm.

Clinical/Scientific Implications

The results of the this study show the superiority of combined docetaxel and carboplatinum over more frequently administered docetaxel alone for advanced NSCLC. Although the toxicity of platinum-based chemotherapy is significant, it's omission from the treatment of advanced NSCLC results in significantly poorer results. The combination of a taxane and platinum-based drug remains one of the standards for first-line treatment of advanced NSCLC.

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