Improved Survival Rates After Re-irradiation, Chemotherapy for Recurring Head, Neck Cancer

Website: http://www.sic2004.org/

Newswise — The diagnosis of head and neck cancer can be devastating to the patient and the family. What can be more disheartening is the discovery of a recurrence of the disease. Patients with locally recurrent disease or a new head and neck cancer in a previously irradiated field have few treatment options available if they are unable to have salvage surgery. Consequently, the median survival for patients treated with chemotherapy alone is six to eight months and two-year survival rates typically are less than 35 percent. Experts in head and neck surgery and oncology set out to examine if treatment options could improve survival rates for those patients with recurrent or new head and neck cancer who had previously been irradiated. The goals of RTOG 99-11 were to: (1) Estimate the median and one-year disease-free and overall survival rates of treated patients; (2) Identify and estimate the incidence rate of acute and late toxicities associated with combined chemotherapy and re-irradiation in patients with recurrent squamous cell cancer of the head and neck; and (3) Determine the pattern of disease progression in recurrent disease patients treated with chemoradiotherapy.

RTOG 99-11, a national Phase II study, has just been completed and the findings are available to the medical community. The authors of "RTOG 99-11: Phase II Study of Concurrent Chemotherapy and Re-Irradiation for Recurrent Head & Neck Cancer," are Eric M. Horwitz MD, C.J. Langer, and N. Nicolaou, from the Fox Chase Cancer Center, Departments of Radiation and Medical Oncology; J. Harris from the Radiation Therapy Oncology Group, Philadelphia, PA; and W.J. Curran, at Thomas Jefferson University, all in Philadelphia, PA; and M. Kies and K. Kian Ang at the M.D. Anderson Cancer Center, Houston, TX; and S.J. Wong, from the Medical College of Wisconsin, Milwaukee, WI. Their findings will be presented at the 6th International Conference on Head and Neck Cancer, being held August 7-11, 2004, at the Wardman Park Marriott in Washington, DC.

Methodology: For inclusion into this study, head and neck cancer patients must have had a recurrent squamous cell cancer of the head and neck or second primary tumors within a previously radiated field; a measurable tumor, larger than 75 percent of tumor volume previously treated to 45-75 Gee; six months must have elapsed from prior radiation therapy; adequate marrow, hepatic, and renal function; and no evidence of distant metastases. Additionally, the entire tumor volume must be included in treatment field without exceeding total cord dose of 50 Gee; no other concurrent invasive malignancies could present as well as no significant co-morbidities which would impair tolerance to treatment.

Patients were treated with split course hyperfractionated RT (60 Gy total: 1.5 Gee/fraction BID X 5d every two weeks X four weeks). Patients also received chemotherapy including DDP 15 mg/m2 IV daily X 5 and paclitaxel 20 mg/m2 IV daily X 5 Q two weeks X four. G-CSF support was administered day six through 13 of each two week cycle. Head and neck cancer sites studied were the oral cavity, n=27 (27 percent); oropharynx, 40 (40 percent); hypopharynx, n=12 (12 percent); larynx, n=10, (10 percent); and other, n=10 (10 percent).

Results: The study enrolled 105 Patients between March 30, 2000, and June 6, 2003. The first 60 eligible patients, median age of 59 with a potential one-year follow-up, were analyzed. Some 72 percent received radiation therapy per protocol or with acceptable variation; 77 percent received all four scheduled cycles of chemotherapy. The median survival for the study subjects was 13 months. One year survival was achieved by 53.2 percent of the test subjects; 27.5 percent achieved two-year survival. Median follow-up for surviving patients was 26.1 months.

From the treatments, the researchers found that (1) Grade > 4 acute toxicity occurred in 30 percent; (2) Grade > 4 acute non-hematologic toxicity occurred in 10 percent; (3) There were two Grade 5 (fatal) toxicities in the acute period (dehydration, pneumonitis) and two late Grade 5 toxicities attributable to carotid hemorrhage. All in all, of the entire population of 105 patients, there were seven fatal toxicities (seven percent).

Conclusions: From this national study of concurrent re-irradiation and chemotherapy, the authors conclude that:

Median survival and one-year and two-year survival rates for split course hyperfractionated re-irradiation and chemotherapy for patients treated on RTOG 99-11 are promising and generally exceed results observed with chemotherapy alone.

Despite significant toxicity, hyperfractionated split course re-irradiation and concurrent cisplatin and paclitaxel chemotherapy demonstrates promising results for this select patient population.

Toxicity is substantial, with a high incidence of Grade 5 toxicity and a 40 percent incidence of late Grade > 3 toxicity.

Patients with second primary tumors or greater than 36 months elapsed from prior treatments fared no better than patients with recurrent disease or less than 36 months from prior treatments.

The authors suggest that a phase III trial directly comparing chemotherapy alone to concurrent CT/RT is warranted with close attention to quality-adjusted survival.