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

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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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