ATLANTA—The TPF induction regimen-docetaxel (Taxotere), cisplatin(Drug information on cisplatin), fluorouracil(Drug information on fluorouracil) (5-FU)—followed by carboplatin(Drug information on carboplatin)-based chemoradiotherapy (CRT) is a "new acceptable standard of care" for locally advanced squamous cell carcinoma of the head and neck (SCCHN), Marshall Posner, MD, of Harvard Medical School, said at a special session of the American Society of Clinical Oncology 42nd Annual Meeting.
The statement is based on the survival advantage shown in the ongoing analysis of TAX 324, a multicenter, randomized phase III sequential trial comparing induction TPF vs PF, followed by carboplatin-based CRT and then surgery as needed.
Advantages of induction chemotherapy followed by CRT over standard concurrent CRT include allowing lower-intensity radiation, more tolerable chemotherapy, and reduced incidence (2%) of subsequent stomach tube dependence, Dr. Posner said.
Patients in TAX 324 had stage III/IV SCCHN (stage IV 82.5%); over half had tumors of the oropharynx (52.5%). Tumors were either resectable with low curability (30% or less) or unresectable. TPF consisted of docetaxel(Drug information on docetaxel) 75 mg/m2, cisplatin 100 mg/m2, 5-FU 1,000 mg/m2 on days 1 to 4 with prophylactic antibiotics on days 5 to 15; PF included cisplatin and 5-FU at the same dosages as above on days 1 to 5; both regimens were given every 3 weeks for 3 cycles. The intent-to-treat population included 255 TPF and 246 PF patients, with 494 patients ultimately receiving chemotherapy, and 386 (78%) receiving CRT per protocol.
Median survival, after median follow-up of 42 months, is 30.1 months in the PF group (53% have died) and at 70.6+ months has not yet been reached in the TPF group (41% have died). Kaplan-Meir 3-year survival (with 72% of patients available for analysis) is 48% in the PF group and 62% for TPF. "That's a 30% reduction in mortality with TPF," Dr. Posner said (hazard ratio 0.70, P = .0058). Progression-free survival at 3-years is 37% for PF and 49% for TPF (P = .004).
Overall response rates after induction chemotherapy and CRT showed favorable trends for TPF: 77% vs 72% for PF (P = .21), with complete response rates of 35% and 28%, respectively (P = .08).
Grade 3-4 stomatitis during chemotherapy was lower with TPF (27% vs 21%), and neutropenia was higher (56% vs 84%), but with protocol-mandated antibiotics, febrile neutropenia and neutropenic infection were similar between groups (7%/9% vs 12%/12%).
