Induction chemotherapy followed by concomitant chemoradiation therapy in advanced head and neck cancer: a phase II study for organ-sparing purposes evaluating feasibility, effectiveness and toxicity.

The purpose of the study was to assess response rate, clinical outcome, organ/function preservation and toxicity in head and neck cancer patients treated with induction chemotherapy followed by concomitant chemoradiotherapy and, when necessary, limited surgery. The study design was a phase II non-randomized trial in hospitalized patients setting. The treatment plan consisted of 3 cycles of induction chemotherapy with cisplatin, fluorouracil (5-FU), l-leucovorin and interferon alpha2b (PFL-IFN) followed by 7 cycles of 5-FU, hydroxyurea and concomitant radiation for 5 days (FHX) for a total radiation dose of 70 Gy. 13 Cis-retinoic acid was added to treatment regimen for chemoprevention and a systematic prophylaxis of mucositis was administered to all patients during FHX. Conservative surgical resection was reserved to patients with no optimal response (PR > or =70%), whereas radical surgery was performed as salvage treatment. Twenty-six patients were treated at one institution: more than 90% had stage IV disease and only 19.2% had laryngeal cancer. Eighty-one percent of patients had performance status 0 and 23.1% of patients had >5% weight loss at the start of treatment. Nineteen patients were analyzed for response to PFL-IFN: 3/19 (15.8%) patients achieved a CR and 7/19 (36.8%) achieved a PR for an ORR of 52.6%. FHX was administered on protocol to 12 patients: 6 patients (50%) had CR, 1 patient (8.3%) had PR for an ORR of 58.3%, 2 patients (16.7%) had SD and 3 patients (25%) had PD. At the completion of FHX, no patient underwent local therapy according to treatment plan. At a median follow-up time of 13.5 months (range 1-28+) at June 2001, among 26 patients enrolled 12 (46.1%) were still alive and 9 (75%) of them were progression-free. The median duration of response was 9 months (range 0-25+), the median progression-free survival was 10.5 months (range 0-28+), the median overall survival time was 9 months (range 1-22). The toxicity was significant and consisted mainly of mucositis and, to a lesser extent, neutropenia/thrombocytopenia. In the present study, the low serum levels of leptin and the high serum levels of proinflammatory cytokines in advanced stage cancer patients were confirmed. In conclusion, this sequential induction chemotherapy and chemoradiotherapy program has been found moderately active and significantly toxic; moreover, the long overall treatment duration must be taken into consideration. For these reasons, this regimen could not be recommended for a phase III randomized study.

Six-week induction chemotherapy followed by concomitant chemoradiation therapy in stage IV head and neck cancer: a phase II study with organ-sparing purposes.

The purpose of the study was to assess response rate, clinical outcome, organ/function preservation and toxicity in head and neck cancer patients treated with induction chemotherapy followed by concomitant chemoradiotherapy and, when necessary, limited surgery. The study was a phase II non-randomized trial. Induction chemotherapy consisted of 6 weekly doses of carboplatin at AUC of 2 and docetaxel 30 mg/m(2) (1 h) followed by 5 cycles of docetaxel 25 mg/m(2)/day 1, 5-FU 600 mg/m(2) c.i. days 1-5, hydroxyurea 500 mg orally every 12 h for 11 and concomitant twice daily radiation therapy at 150 cGy/fraction given every other week per 5 cycles (TFHX), for a total radiation dose of 75 Gy. 13 cis-retinoic acid was administered for chemoprevention and systematic prophylaxis of mucositis with systemic amifostine and local GM-CSF was administered to all patients during TFHX. Conservative surgical resection was reserved to patients with no optimal response (PR > or =70%), whereas radical surgery was performed as salvage treatment. Thirteen patients (mean age 54.9 years, range 44-62; 12/13 site oropharynx, all stage IV) were enrolled: 31% of patients had ECOG performance status (PS) 0 and 69% had PS 1. Response to induction chemotherapy was analyzed in 12 patients: 2/12 (16.7%) achieved a partial response (PR) for an overall response (ORR) of 16.7%, 10/12 (83.3%) achieved stable disease (SD). TFHX was administered to 7 patients: 2 patients (28.6%) had complete remission (CR), 1 patient (14.3%) had PR for an ORR of 42.9%, 3 patients (42.8%) had SD and 1 patient (14.3%) had PD. At the completion of TFHX, 1 patient underwent local therapy. The toxicity was mild and consisted in: grade 3/4 neutropenia (7.7%), anemia (23.1%), diarrhea (15.4%), mucositis (7.7%), neurotoxicity (7.7%) during induction chemotherapy. During TFHX only 42.8% of grade 3/4 mucositis was observed. All patients spared organ/function. In conclusion, this regimen has been found feasible for its acceptable toxicity, particularly mucositis. However, the overall response rate and the data on survival were not satisfactory.