RTOG 0017: A Phase I Trial of Concurrent Gemcitabine/Carboplatin or Gemcitabine/Paclitaxel and Radiation Therapy ('Ping-Pong Trial') Followed By Adjuvant Chemotherapy for Patients with Favorable Prognosis Inoperable Stage IIIA/B Non-small Cell Lung Cancer
التفاصيل البيبلوغرافية
العنوان:
RTOG 0017: A Phase I Trial of Concurrent Gemcitabine/Carboplatin or Gemcitabine/Paclitaxel and Radiation Therapy ('Ping-Pong Trial') Followed By Adjuvant Chemotherapy for Patients with Favorable Prognosis Inoperable Stage IIIA/B Non-small Cell Lung Cancer
Purpose: The optimal dose of gemcitabine that can be used with concurrent radiation therapy for locally advanced non-small cell lung cancer has not been well defined. This trial addresses this question in an alternating sequence “ping-pong” design trial to find the maximum tolerated dose (MTD) for gemcitabine/carboplatin (Sequence A) or gemcitabine/paclitaxel (Sequence B) and thoracic radiation therapy followed by adjuvant gemcitabine/carboplatin chemotherapy. Patients and Methods: Thirty-five patients with histologically confirmed Stage IIIA/B non-small cell lung cancer were entered into two separate sequences, each with multiple cohorts. A dose level was considered acceptable if, of the first six eligible patients on each cohort, fewer than three experienced dose limiting toxicities. Results: Sequence B of this 2 sequence “ping-pong” trial closed early due to toxicity in cohort 2 (gemcitabine 300 mg/m 2 /wk and paclitaxel 30 mg/m 2 /wk). On Sequence A, the MTD was the cohort 5 dose: gemcitabine 450 mg/m 2 /wk and carboplatin 2 area under curve (AUC) concurrently with thoracic radiation. Cohort 7 (gemcitabine 600 mg/m 2 /wk and carboplatin 2 AUC) showed 4 dose limiting toxicities: 2 grade 3 esophagitis; one grade 3 febrile neutropenia; and one grade 4 neutropenia. Conclusion: Concurrent gemcitabine/paclitaxel chemoradiation regimen followed by adjuvant gemcitabine/carboplatin produced excessive toxicity at the lowest tested dose combination and was not suitable for further study in this trial. Meanwhile, the MTD of concurrent gemcitabine/carboplatin chemoradiation was determined to be gemcitabine 450 mg/m 2 and carboplatin AUC-2. This combination was found to be tolerable. Although not a primary end point, survival results are summarized as well.
