H. Wanebo

Paclitaxel and concurrent radiation for locally advanced pancreatic and gastric cancer: a phase I study.

PURPOSE To determine the maximum-tolerated dose (MTD), dose-limiting toxicities, and potential antitumor activity of weekly paclitaxel with concurrent radiation (RT) for locally advanced pancreatic and gastric cancer. PATIENTS AND METHODS Thirty-four patients with locally advanced adenocarcinoma of the pancreas or stomach were studied. The initial dose of paclitaxel was 30 mg/m2 by 3-hour intravenous (I.V.) infusion repeated every week for 6 weeks with 50 Gy RT. Doses were escalated at 10-mg/m2 increments in successive cohorts of three new patients until dose-limiting toxicity was observed. RESULTS The dose-limiting toxicities at 60 mg/m2/wk were abdominal pain within the RT field, nausea, and anorexia. Of 23 patients with assessable disease, 11 (seven with gastric, four with pancreatic cancer) had objective responses for an overall response rate of 48%. CONCLUSION Concurrent paclitaxel with upper abdominal RT is well tolerated at dosages that have substantial activity. A phase II trial of neoadjuvant paclitaxel and RT at the MTD of 50 mg/m2/wk is underway.

Paclitaxel and concurrent radiation for gastric cancer

PURPOSE To determine the activity and toxicity of paclitaxel and concurrent radiation for gastric cancer. METHODS AND MATERIALS Twenty-seven patients were studied. Twenty-five had proximal gastric cancers, two had distal cancers. Eight had esophageal extension, 6 had celiac adenopathy, and 7 had retroperitoneal adenopathy. Patients received paclitaxel, 50 mg/m(2) by 3-hour intravenous (IV) infusion, weekly, on days 1, 8, 15, 22, and 29. Radiation was administered concurrently to a total dose of 45.0 Gy, in 1.80 Gy fractions, for 25 treatments. Patients who were medically or surgically inoperable received a sixth week of paclitaxel with a radiation boost to 50.4 Gy. RESULTS Esophagitis and gastritis were the most important toxicities, Grade 3 in four patients (15%), and Grade 4 in three patients (11%). Five patients (19%) had Grade 3 nausea. The overall response rate was 56%, including three patients (11%) with a complete response. The 2-year progression-free and overall survival rates were 29% and 31%, respectively. CONCLUSION Concurrent paclitaxel and radiation demonstrates substantial local-regional activity in gastric cancer. Future investigations combining paclitaxel and radiation with other local-regional and systemic treatments are warranted.

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a toxicity analysis.

Objective:To determine the feasibility and toxicity of the addition of cetuximab to paclitaxel, carboplatin, and concurrent radiation for patients with head and neck cancer. Materials and Methods:Patients with stage III or IV locally advanced squamous cell cancer of the head and neck, without distant organ metastases, were eligible. Patients received 4 weeks of induction cetuximab followed by weekly cetuximab, paclitaxel, carboplatin, and concurrent radiation. Results:Thirty-two patients were assessable for chemoradiation toxicities. Grade 3 and grade 4 mucositis occurred in 53% and 16% of patients, respectively. Grade 3 and grade 4 radiation dermatitis occurred in 44% and 9% of patients, respectively. Grade 3/4 radiation dermatitis was associated with the use of intensity modulated radiation therapy (64% vs.14%, respectively, P < 0.0001). Grade 3 and grade 4 cetuximab associated acneiform rash developed in 6% and 3% of patients. Overall 21 patients (66%) had any grade 3 toxicity and 10 patients (31%) had any grade 4 toxicity. The percentages of the intended total dose delivered of carboplatin, cetuximab, paclitaxel, and radiation were 86%, 89%, 89%, and 96%, respectively. Conclusion:Cetuximab, when combined with paclitaxel, carboplatin and intensity modulated radiation therapy, increases dermatologic toxicity but does not increase mucosal toxicity as compared with previous Brown University Oncology Group studies of paclitaxel, carboplatin, and conventional radiation for patients with head and neck cancer.

Cetuximab, paclitaxel, carboplatin, and radiation for head and neck cancer: a survival analysis of a Brown University Oncology Group phase II study.

Objectives:To assess the effect on progression-free and overall survival from the addition of cetuximab to paclitaxel-based chemoradiation for patients with squamous cell head and neck cancer from Brown University Oncology Group studies. Methods:BrUOG HN-204 patients with stage III or IV locally advanced squamous cell cancer of the head and neck without distant organ metastases received 4 weeks of induction cetuximab followed by weekly cetuximab, paclitaxel, carboplatin, and concurrent radiation. Recurrence and survival data were compared with previous Brown University studies utilizing the same paclitaxel-based chemoradiation with and without induction chemotherapy. Results:The progression-free survival and overall survival at 3 years for all 37 patients initiating chemoradiation was 54% and 57%, respectively. All surviving patients were followed for at least 3 years and the median follow-up is 4.4 years. Of 14 patients who recurred within 3 years, 7 patients recurred locally only, 5 had a systemic recurrence, and 2 recurred both locally and systemically. Conclusions:The addition of cetuximab to paclitaxel, carboplatin, and radiation achieves overall survival that is virtually identical to prior Brown University Oncology Group studies of paclitaxel-based chemoradiation without cetuximab. Improvements in locoregional control are needed despite the use of 3 agents to enhance the effects of radiation.

Phase I/II study of induction weekly paclitaxel, ifosfamide and carboplatin (PIC) followed by chemoradiotherapy (CRT) in advanced head and neck squamous cell cancers (HN-SCC)

5602 Background: CRT for Stage III/IVA HN-SCC improves local control and survival. Multiple reports show higher rates of systemic than local failures. We are performing this outpatient phase I/II study to determine the optimal dose and efficacy of induction weekly PIC chemotherapy in these patients (pts). METHODS Pts were stratified as operable versus inoperable. In the phase I portion, escalating doses of Paclitaxel (P) 60, 80 or 100 mg/m2 with Ifosfamide (I) 1000mg/m2 and Carboplatin (C) AUC=2 were given weekly for 6 of 8 weeks. Mesna 1000 mg/m2 was co-administered with I. CRT consisted of weekly P 40mg/m2 and C AUC=1 with RT 1.8 Gy/day (total 66-72 Gy). Inoperable pts received 8 weeks CRT while operable pts underwent primary site biopsy after 5 weeks. Biopsy positive pts underwent surgery and post op RT. Biopsy negative pts received 3 more weeks of CRT. RESULTS Of 15 pts enrolled, 1 refused therapy, 1 had lung metastases, and 1 had major dosing error. The rest (M= 9, F= 3) had a median age of 55 yrs (range 30-78). PS was 0 (n=10) or 1 (n=2). TNM stages were III (n= 5) or IV (n= 7). Dose levels 1 and 3 were well tolerated. Level 2 was expanded due to 1 pt receiving < 80% planned dose. Major toxicities are tabulated below. Phase I responses after completing PIC and CRT were: primary site path CR in 11 pts (92%) & SD in 1 pt (8%); residual nodal disease in 1 pt (8%) at neck dissection. Using the level 3 dose as the phase II dose, an additional 18 pts have finished PIC. CONCLUSIONS Outpatient weekly dose intense induction chemotherapy with PIC is well tolerated with a favorable toxicity profile. Patient accrual is continuing at the phase II dose of P 100 mg/m2, I 1000mg/m2 and C AUC=2 given weekly for 6 of 8 weeks. Initial efficacy results will be available at the time of presentation. [Figure: see text] No significant financial relationships to disclose.

Use of restaging primary site biopsy to optimize selection of primary therapy in high stage (III/IV) squamous cancer

6042 Background: A consecutive series of neoadjuvant protocols has focused on restaging re-biopsy to select therapy of Stage III/IV squamous cancer since 1995. Patients with positive restaging biopsy have subsequent resection whereas those having a negative re-biopsy have completion chemo- radiation therapy of primary site to total dose 68–72cGy. We are currently reporting the benefit of giving induction chemotherapy prior to chemoradiation. Methods: Initial protocols (H&N 53& 67) utilized concurrent preoperative Paclitaxel (P) (60mg/M² or 40mg/M2) + Carboplatin (AUC) + RT (45G) 67(64 evaluable pts). Subsequent studies (H&N79) utilized induction chemo (P 135mg/M², C (2AUC) weekly x 6 followed by chemoradiation therapy P 40 C (1AUC) + 45 Gy (H&N79) 32 pts (13 operable). Results: Protocols, 53 & 67 induced a complete pathologic response in 70% vs. a 52% clinically determined CR permitting completion radiation with primary site preservation. Neck dissection (ND) revealed persistent disease in 37% confirming ...