A Phase II Study of Induction Docetaxel/Cisplatin with rhG-CSF and Concurrent Pulsed Docetaxel Chemoradiation for Stage III Non-Small Cell Lung Cancer (NSCLC)

Abstract

Purpose/Objective: Both local failure and distant metastasis remain the main causes of poor survival outcome in the era of combined chemoradiation (CRT) for stage III NSCLC. A previous institutional study employing pulsed low-dose paclitaxel radiosensitizing chemoradiation for stage III NSCLC has yielded a 100% gross tumor response rate and a 98% local tumor control rate for large tumors of stage III NSCLC. The remarkable gross tumor response rate and local control were associated with only a modest survival gain when compared with historical results (Clin Cancer Res 9: 969–975, 2003). We report a subsequent institutional protocol designed to target distant micro-metastasis by one-cycle of full-dose, two-drug induction chemotherapy (CT) up-front, without further delay of local therapy. Induction chemotherapy is followed by low-dose sensitizing docetaxel (Doc) chemoradiation for gross chest tumors. Materials/Methods: Patients with inoperable stage III NSCLC were eligible. Induction CT consisted of docetaxel 75mg/m2 and cisplatin (Cis) 75mg/m2 on day 1, followed by rhG-CSF (150 μg/m2 s.q. days 2–10). Concurrent chemoradiation started 3–6 weeks after induction CT. The originally planned Doc dose of 12 mg/m2, twice weekly with daily RT, was lowered to 10 mg/m2 midway through the study due to toxicity. RT dose was 64.8 Gy to gross tumor and 45–57.6 Gy to subclinical disease. All patients enrolled were followed for toxicity. Results: Twenty-two patients have been enrolled since 2/2002 and 2 are currently under treatment. All received induction CT, except 2 with an anaphylactic reaction to Doc. Fourteen completed both induction CT and CRT. Four did not complete therapy due to: Doc intolerance in 1, intercurrent illness in 1, and disease progression during therapy in 2. Toxicities of induction CT were: grade 3 allergic reaction (10%), grade 3 infection with normal ANC (20%), grade 3 nausea/vomiting (10%), grade 3 hypertension (5%) along with grade 3 hyperglycemia (5%), grade 4 hyperglycemia (5%), grade 3 headache (5%), grade 3 fatigue (10%), and grade 4 fatigue (5%) along with grade 3 dyspnea (5%). There was no grade 3 or 4 hematologic toxicity from induction CT. Toxicity from concurrent CRT was primarily esophagitis. Fifty percent of patients (4/8) who completed chemoradiation treatment at the initial twice-weekly Doc dose of 12 mg/m2 developed grade 3 esophagitis. Subsequent subjects received reduced Doc dose to 10 mg/m2 and no further grade 3 esophagitis was observed after Doc dose reduction. Other grade 3 toxicities from CRT were fatigue (14%), loss of appetite (14%), flushing (7%), chest pain (7%), diarrhea (7%), and nausea & vomiting (28%). No patient developed grade 3 or 4 pneumonitis or any grade 4 toxicity. Conclusions: Induction chemoradiation of one-cycle, full-dose Doc/cisplatin with rhG-CSF followed by concurrent pulsed low-dose Doc CRT is well tolerated with low hematologic toxicity. 50% of pts in the study experienced grade 3 esophageal toxicity at Doc dose of 12 mg/m2 from CRT, although published MTD of twice-weekly Doc CRT was 15 mg/m2. Grade 3 esophagitis was not observed after Doc dose reduction to 10 mg/m2. We will be analyzing the tumor response and preliminary survival end point of this study. The patterns of failure will be compared with the previous institutional study of pulsed low-dose paclitaxel CRT without the induction CT to derive information of any benefit from the addition of one-cycle induction chemotherapy in targeting distant micrometastasis. This study is partially supported by Aventis Pharmaceuticals.