A Phase II Non Randomized Trial of Sequential Chemoradiation (Gemcitabine/Carboplatin Plus Thoracic Irradiation) in Patients with Unresectable Stage III Non Small Cell Lung Cancer (NSCLC)

Purpose: The objectives of this phase II prospective non randomized study were to determine the overall response rate in previously untreated patients with locally advanced unresectable stage III NSCLC after treatment with sequential chemoradiation (gemcitabine/carboplatin plus thoracic irradiation) and to identify the median survival, overall, progression free survivals, predictors of survival and toxicity profile. Patients and Methods: Chemonaive patients (n=45) with histological or cytological diagnosis of stage III unresectable NSCLC received gemcitabine lgm/m2 infusion over 30 minutes on day 1 and 8 and carboplatin AUC-5 infusion over an hour on day 1 after the gemcitabine infusion. Both drugs were given in 21 day cycle for a maximum of 4 cycles. Patients in complete remission (CR), partial remission (PR) or even stable disease (SD) after 4 cycles, (n=37) received external beam irradiation 56-60 Gy to the primary site and regional nodes 2 weeks after the last cycle of chemotherapy. All patients had WHO performance status of 2, adequate bone marrow, normal liver and kidney profiles with life expectancy of more than 6 months. were enrolled at Kasr El-Aini Centre of Clinical Oncology and Nuclear Medicine (NEMROCK) and Agouza Hospital. The Median age was 48 years (range 28-68 years). All 45 patients were evaluable for response and toxicity. CR was achieved in 4 patients (9%) and 17 patients (38%) achieved PR for an overall response rate of 47% (95% CI, 22.7-59.7%). Sixteen patients (35.5%) had stable disease while 8 patients (17.5%) had disease progression. The median duration of response was 8 months (range 3-15 months), median time to progression (TTP) was 10 months (range 4-14 months) and median (OAS) survival was 14 months (range 3-20 months). Weight loss and performance status were the most common independent survival predictors (p = 0.02 and 0.035 respectively). The predominant toxicity was hematological with grade 3 leucopenia reported in 12 patients (27%) and grade 2 thrombocytopenia in 16 patients (35%), while the most common non hematological toxicity was radiation esophagitis, grade 1 in 20 patients (54%) and grade 2 in 12 patients (32%). Conclusion: As there is no clear advantage of sequential followed by concurrent chemoradiation over sequential chemoradiation alone, the present study showed that sequential chemoradiation using the combination Gemcitabine / Carboplatin and thoracic irradiation could be an effective well tolerated treatment option for patients with locally advanced unresectable stage III NSCLC with lower toxicity profile especially for those presented with initial good performancev status.