Concurrent split course hyperfractionated radiotherapy (Hfx RT), cisplatin (DDP) and paclitaxel (P) in patients with recurrent, previously irradiated squamous cell carcinoma of the head and neck (SCCHN): Update of RTOG 9911.

5577 Background: Chemotherapy (CTx) alone (eg. DDP, 5FU) remains the standard therapy for recurrent SCCHN, but yields median survival times (MST) of only 8-10 mos & 1 yr survival (OS) of ≤ 35% at best. For limited relapse or new unresectable SCCHN within previous RT portals, a potential role for re-irradiation combined with radiosensitizing CTx, exists. Based on a prior phase I trial of split course HFx RT/ DDP/ P, in which we observed a response rate of 55% & ≥ 2 yr progression-free survival (PFS) in 5 of 31 pts (ASCO 1999, A-1551), RTOG initiated a phase II trial.,Eligibility stipulated recurrent SCCHN or second 1° tumors (SPT) in a previous RT field with ≥ 75% of tumor volume previously treated to 45 Gy-75 Gy; ≥ 6 mos elapsed from prior RT, ECOG PS 0-1; ANC ≥1500, plts ≥ 100K, bili ≤1.5 mg/dl, creat ≤ 1.5 mg/dl, & absence of distant mets. Pts received HFx RT (1.5 Gy/Fx BID x 5d every 2 wks x 4), in combination with DDP 15 mg/m IV QD x 5 & P 20 mg/m IV QD x 5 q 2 wks x 4. G-CSF was given days 6 through 13 of each 2 wk cycle.,105 pts (median age 60; 77% male; 66% PS 1) were entered between 3/00 & 6/03; 99 proved eligible. 23% had SPTs. Oropharynx (40%) & oral cavity (27%) were the predominant 1° sites. Median prior RT dose was 65.4 Gy (range, 45-75 Gy), median time from prior RT 40 mos. 74% of pts received all 4 scheduled cycles of chemo; 69% received RT as planned (median dose 60 Gy). Gr ≥ 4 acute toxicity (tox) occurred in 28%, gr ≥ 3 leukopenia in 30%, gr ≥ 3 anemia in 21%, and gr ≥ 3 GI toxicity in 48%. Delayed osteoradionecrosis occurred in 4%. There were 8 fatal (Gr 5) toxicities: 5 in the acute period (dehydration, pneumonitis, neutropenic fever [2], CVA) & 3 late (carotid hemorrhage in 2). At a median follow-up of 23.6 mos, MST is 12.1 mos with est. 1- & 2-yr OS rates of 50.2% (95% CI: 40.0, 59.6) & 25.9% (17.3, 35.3). Median & 1-yr PFS are 7.8 mos & 35% (CI 25.7, 44.4) Conclusions: Despite a fairly high incidence of Gr 5 tox, the 1- & 2-yr OS rates for split course HFxRT/DDP/P exceed results generally seen with chemotherapy alone. A phase III trial directly comparing CTx alone to concurrent CTx & re-irradiation with survival as the 1° enpoint is planned. [Table: see text].