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Use of Low-dose Fractionated Radiation (LDFRT) as a Chemosensitizer of Neoadjuvant Paclitaxel (P) and Carboplatin (CBCDA) for Locally Advanced Squamous Cell Carcinoma of the Head and Neck (SCCHN) - Results of a New Treatment Paradigm

Reviewer: Mary Kara Bucci, MD
The Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 18 de mayo del 2002

Presenter: Susanne Arnold
Presenter's Affiliation: Markey Cancer Center, Lexington , Kentucky
Type of Session: Poster

Background

Radiation resistance is a major cause of treatment failure in squamous cell cancer of the head and neck (SCCHN). Low dose fractionated radiation (LDFRT), defined as doses < 100 cGy, induces an initial phase of hypersensitivity in vitro. This hypersensitivity is thought to be due to the induction of apoptosis without the initiation of pro-survival pathways that are seen at higher radiation doses. LDFRT in combination with paclitaxel has been shown to enhance cell kill compared to either paclitaxel or LDFRT alone. LDFRT plus paclitaxel may provide a way to overcome radiation resistance. The aim of this study is to assess the safety and toxicity of LDFRT in combination with paclitaxel and carboplatin.

Materials and Methods

• 38 patients with advanced (Stage III or IV) SCCHN were enrolled on this trial.
• Patients received two cycles of induction therapy with paclitaxel (225 mg/m2 over 3 hours) and carboplatin (AUC of 6 over 30 minutes) every 3 weeks.
• On day 1 and day 2 of chemotherapy cycle, patients received two fractions of 80 cGy, separated by at least 6 hours. The first fraction was given within 2 hours of completing chemotherapy.
• Following this induction therapy, patients went on to received definitive treatment with surgery or radiation.

Results

• 37 patients are evaluable for response (one patient refused further treatment or evaluaion after one dose of chemotherapy).
• The overall rate of grade 3 toxicity was 24%; the rate of grade 4 toxicity was 37%.
• 5 patients (13%) experienced grade 3 neutropenia and 14 patients (37%) experienced grade 4 neutropenia.
• 5 patients developed grade 3 skin toxicity, 3 patients had a grade 3 allergic reaction, and 3 patients had grade 3 pulmonary toxicity.
• There was no grade 3/4 mucositis or radiation skin changes.
• At the primary tumor site, 15 patients experienced a complete response (CR)and 18 patients experienced a partial response (PR), for an overall response rate at the primary site of disease of 89% (33/37 patients).
• Of 30 patients evaluable for response at nodal sites, 10 patients had a CR, and 10 had a PR, for an overall response rate of 67% (20/30 patients).
• No patient progressed at the primary site, and 1 patient progressed in lymph nodes after the first cycle of chemotherapy.
• With a median follow-up of 6 months (range 1-18 months), 33 patients are alive and well, 3 have known disease, and 2 have died of their disease.

Author's Conclusions

• LDFRT with combination paclitaxel/carboplatin is well-tolerated and effective, with a response rate of 89%.
• Induction LDFRT plus chemotherapy may provide a way to down-stage tumors, and therefore improve the rate of organ-sparing treatment.

Clinical/Scientific Implications

The hypersensitivity induced by low dose fractionated radiation is enhanced by the addition of chemotherapy in vitro. This approach has not previously been explored clinically, but may provide a novel way to improve both survival as well as organ-sparing in advanced stage SCCHN. Further studies, including a direct comparison of this approach to standard therapy, are indicated.

Oncolink's ASCO Coverage made possible by an unrestricted Educational Grant from Bristol-Myers Squibb Oncology.