Phase II and pharmacokinetic (pk) study of induction docetaxel/cisplatin followed by pulsed docetaxel chemoradiation for stage III non-small cell lung cancer (NSCLC)

18142 Background: We have previously reported that docetaxel (Doc) demonstrates longer G2/M arrest and better synergistic effects with irradiation when compared with paclitaxel in human lung cancer cell lines. We designed a phase II clinical study targeting micrometastasis using upfront induction chemotherapy (CT) with Doc/cisplatin (CP) followed by sensitizing Doc chemoradiation (CRT) for patients (pts) with stage III NSCLC. Methods: Pts with inoperable stage III NSCLC were eligible. Induction CT consisted of Doc 75 mg/m2 and CP 75 mg/m2 on d 1 followed by rhG-CSF (150 ug/m2 sq on d 2 to 10). The CRT consisted of sensitizing Doc 12 mg/m2 twice per wk with daily RT (64.8 Gy to gross tumors and 45–57.6 Gy to subclinical disease). PK studies of Doc were performed during CT and CRT in each pt. The clearance (CL) and area under the plasma concentration versus time curve (AUC) were estimated. Results: 26 pts were enrolled and 16 completed study. Overall response rate was 69% [50% (8/16) PR and19% (3/16) CR]. 2-year survival was 57 %. During induction CT, primary grade (G) 3 toxicities were allergic reaction (10%), non-neutropenic infection (20%), nausea/vomiting (N/V) (10%), fatigue (10%), hypertension (5%) hyperglycemia (5%), dyspnea (5%) & fatigue (5%). There was no G3/4 hematologic toxicity. During CRT, 50% (4/8) of pts developed G3 esophagitis after Doc at 12 mg/m2. The next 8 pts received Doc at 10 mg/m2 with only 1 pt developing G3 esophagitis. Other G3 toxicities from CRT were N/V (28%), fatigue (14%), loss of appetite (14%), flushing (7%), chest pain (7%), & diarrhea (7%). No G3 or 4 pneumonitis or any G4 toxicity. Mean ± SD Doc CL at 75 and 10 mg/m2 were 20 ± 5 and 22 ± 10 L/h/m2, respectively. Ratio of Doc CL at 75 to 10 mg/m2 within a pt was 1.0 ± 0.4. Doc AUC at 75 and 10 mg/m2 were 3,933 ± 1,028 and 566 ± 257ng/ml·h, respectively. Conclusions: One-cycle full- dose Doc/CP with rhG-CSF followed by pulsed low-dose Doc CRT is associated with promising antitumor activity and low hematologic toxicity. Grade 3 esophagitis was associated with dose intensity of radiosensitizing Doc, and was minimized by dose reduction. Results suggest that this regimen should be further evaluated in pts with NSCLC. The PK disposition of Doc was similar at 75 and 10 mg/m2. No significant financial relationships to disclose.