Low-dose gemcitabine with radiotherapy in advanced head and neck and thyroid cancer

Introduction : Gemcitabine (GEM) is a nucleoside analogue of deoxycytidine with high activity against solid tumours. In addition GEM is a potent radiation sensitizer. GEM has been evaluated in head and neck cancer, as preclinical activity in this tumour type has been described previously.In order to evaluate the toxicity and efficacy of a combination of radiotherapy and low-dose gemcitabine in locally advanced or recurrent head and neck or thyroid cancer we started a pilot study. Patients and methods : 35 Patients received 200 mg/m² or 100 mg/m² GEM i.v. Once weekly during radiotherapy, single dose 1,8 Gy, total dose : untreated 70 Gy, pre-irradiated patients 26-40 Gy. 31 pt. head and neck, 4 thyroid cancer (2 anaplastic, 1 medullary, 1 folliculary). Median age 59 (30-85) years, 30 male, 15 female, 19 patients first-line treatment, 16 patients pre-irradiated with a median dose of 60 Gy (30-80) radiotherapy. Other pretreatment surgery (17) and chemotherapy (10). Results : The most common side effects were mucositis and erythema. In 17 patients toxicities greater than grade 2 were observed. In 6 patients the administration of gemcitabine was discontinued due to toxicity (3 pts mucositis gr 3, 1 pt skin toxicity gr 3, 2 pts hematologic toxicity gr3). 32/35 patients are evaluable for response, 11 CR, 8 PR, 10 SD, 3 PD. In untreated patients the response rate is 80% vs. 29% in pre-irradiated patients. Interestingly thyroid cancer patients responded well (2/4 PR, 2 SD). After a median follow-up of 29 (3-99) weeks the median time to progression is 20 (1-99) weeks. The median time to progression in patients with first-line treatment is 26 (1-99) weeks vs. 17 (1-92) in pre-irradiated pts. Conclusion : Full dose irradiation in combination with weekly low dose gemcitabine of 100 mg/m²/week is a very feasible, tolerable and effective treatment for locally advanced head and neck and thyroid cancer in patients who are not suitable for cis-platin based chemotherapy. Further evaluation of this schedule seems to be indicated and integration of the excellent local-control rate induced by radiosensitizing gemcitabine into systemic chemotherapy protocols.