Chemotherapy RTOG SWOG Chemotherapy Choice Cisplatin and Docetaxel Cisplatin

Chemotherapy RTOG 0412/ SWOG 0332 Chemotherapy Choice: Cisplatin and Docetaxel Cisplatin was used successfully in INT 0139 Choice of cisplatin allows delivery of same full doses of cisplatin without or with RT Cisplatin/docetaxel as induction chemotherapy has been reported as active and safe in the SAKK study Favorable preliminary toxicity data in combination with RT are available from the pilot SWOG 0022 trial RTOG 0412/ SWOG 0332 Swiss SAKK Trial: Design Multicenter Phase II trial of 90 patients with potentially operable Stage IIIA NSCLC Cisplatin 40 mg/m2 D1,2 Docetaxel 85 mg/m2 D1 Every 3 weeks Surgery RT 60 Gy: positive margins or involved uppermost mediastinal node (Betticher et al, 2003) RTOG 0412/ SWOG 0332 Swiss SAKK Trial: Results Toxicity: 0 Grade 4; 48% Grade 3 Clinical response to induction chemotherapy: 8% CR, 58% PR, 10% PD Resectability rate: 87% (48% R0 resection) pCR 19% (>95% necrosis and fibrosis) of resected MST 27.6 months & 3-yr OS rate (estimated): 34% RTOG 0412/ SWOG 0332 Closed Phase II SWOG 0022 Goal: enroll 90 patients with Stage IIIB NSCLC Cisplatin/docetaxel concurrent with RT No fatal toxicities in 33 patients One Grade 4 toxicity (anemia) Grade >3 RT esophagitis: 4/29=14% RTOG 0412/ SWOG 0332 Japanese Data Cisplatin/Docetaxel with RT in the Definitive and Preoperative Setting Author N Toxicity/ RT Dose Surg Periop. mortality No Pneumon 4.8% (1 death) Survival MST 24 mo Kiura 2003 69 60 Gy IIIA/B Katayama 2004 IIIA/B 22 40-46 Gy 2 Gr2 and 2 Gr3 Yes pneumonitis periop: 0% 3 yr OS 66% RTOG 0412/ SWOG 0332 Rationale for Maintenance Chemotherapy Need for systemic chemotherapy doses in patients at high risk of relapse Supporting evidence: excellent MST (26.0 mo) in SWOG 9504 phase II trial of concurrent CDDP/VP-16 with XRT followed by docetaxel in locally advanced NSCLC large adjuvant chemotherapy trials presented at ASCO 2003/2004 showing benefit to postoperative chemotherapy IALT Phase III Trial CALGB 9633 Japanese Phase III trial NCI C (BR 10 RTOG 0412/ SWOG 0332 Maintenance Chemotherapy Feasibility Study Percentage of patients completing postoperative chemotherapy INT 0139 IALT CALGB 9633 NCIC (BR 10) 58% 74% 85% 59% RTOG 0412/ SWOG 0332 Chemotherapy Details Induction Chemotherapy Alone Cisplatin 75 mg/m2 D1, 22 Docetaxel 75 mg/m2 D1,22 Induction Chemo-RT Cisplatin 50 mg/m2 D1,8,22,29 Docetaxel 20 mg/m2 D1,8,15,22,29 Maintenance Docetaxel 75 mg/m2 D1,22,43 Pegfilgrastim or filgrastim after each docetaxel administration RTOG 0412/ SWOG 0332