Phase II Study: Induction Chemotherapy & Transoral Surgery as Definitive Treatment (Tx) for Locally Advanced Oropharyngeal Squamous Cell Carcinoma (OPSCC): a Novel Approach

Background: The standard of care for OPSCC includes chemoradiation (CRT) or surgery with adjuvant radiation (RT). However, RT is associated with significant life long morbidity. We assessed the efficacy of a two-drug induction regimen, followed by transoral robotic assisted surgery (TORS) & neck dissection for locally advanced OPSCC. Methods: This is an IRB approved single-arm phase II study for untreated stage III or IVA OPSCC patients (pts) with an ECOG \u3c 2 and GFR \u3e50 cc. Induction chemotherapy consisted of cisplatin 75 mg/m2 and taxotere 75 mg/m2 every 21 days for 3 cycles. Tumor shrinkage was examined after each cycle. If the primary tumor was \u3e 80% smaller, pts underwent TORS and neck dissection(s). At post-op visits, flexible laryngoscopy, blood work, and imaging with PET/CT and/or MRI were done. Short and long term toxicity, progression-free survival (PFS) and overall survival (OS), and quality of life (QOL) were evaluated. Results: Nineteen pts were treated and 14 are available for analysis. Thirteen were male, 12 were Caucasian, and 13 were HPV+. Median age at diagnosis was 57. Tumors involved the tonsil (11 pts) and base of tongue (3 pts). Three pts were stage III, and 11 were stage IVA. Tumor size was reduced on average by 58%, 84% and 92% after the 1st, 2nd and 3rd induction cycles respectively. Pathologic complete remission of primary disease occurred in 11 pts and in 7 pts with cervical lymph node disease. Four pts were given dose-reduced chemo and one pt was changed to carboplatin per protocol because of renal dysfunction. Pre vs post tx QOL scores did not change. At a mean follow-up (f/u) of 13 months (range 2.5 to 19.7), 13 pts are alive and well. Three pts recurred, and were treated with salvage CRT. One pt died of metastatic disease. Conclusions: 1) Cisplatin + Taxotere is an effective induction tx for OPSCC, 2) Induction tx followed by transoral & neck resections without RT is a promising tx model for OPSCC. It appears effective while avoiding adverse effects of RT. Longer f/u is required to assess its true efficacy

O-MAX chemotherapy: high activity in metastatic esophagogastric adenocarcinoma and possible relation to subclinical hemolysis.

© 2014 S. Karger AG, Basel. Objectives: Our objectives were to confirm the activity of O-MAX chemotherapy in adenocarcinoma of the stomach and esophagus, particularly the high rate of complete remission (CR) and the relation of subclinical hemolysis to CR. Patients and Methods: Twenty-five patients with metastatic esophagogastric adenocarcinoma were treated with O-MAX. Two developed cancer-related hemolytic-uremic syndrome (C-HUS); both achieved CR. Subsequent patients were monitored for serum haptoglobin for subclinical hemolysis. Results: Median survival was 16.5 months. The objective response rate was 90%, with 38% CR. Three patients achieving CR relapsed in the central nervous system and died (2 without systemic disease). Four patients have remained alive, off therapy, the longest for 20 years. Two patients developed clinical C-HUS and 5 of 8 monitored patients developed subclinical hemolysis based on abnormal serum haptoglobin. Four of the patients with subclinical hemolysis achieved CR. Of the 7 patients developing clinical C-HUS or subclinical hemolysis, 6 (86%) achieved CR. Conclusions: O-MAX appears highly active in esophagogastric adenocarcinoma. A few long-term survivors of metastatic disease are being seen. CR and long-term survival appear to correlate with the development of hemolysis. Although highly promising, these results should be considered only as hypothesis-generating and require confirmation in a prospective trial