Chemotherapy of cancer of the head and neck

Abstract

Single agent chemotherapy employing either hydroxyurea, cyclophosphamide, bleomycin, or methotrexate has been reported to produce objective remissions in 30–40% of patients with advanced epidermoid carcinoma of the head and neck region. Responses are usually incomplete with remission durations of a few months. Methotrexate, the most extensively studied agent, appears to be most effective when used in an intermittent (every 4–7 day) dosage schedule or when used in high dosage followed by leucovorin “rescue.” In some reports, the intra‐arterial administration of these drugs achieved better response rates, but the value of this approach is diminished by the high frequency of lesions that extend beyond the infused arterial supply and the high complication rate of catheterization procedures. Initial studies with dichlo‐romethotrexate, an equipotent analog of methotrexate which is hydroxylated to an inactive form by the liver, suggest that intra‐arterial use of this unique compound may be of value. Several studies indicate that the use of drugs in combination with radiotherapy may achieve greater tumor regression and longer response durations than radiotherapy alone; however, more controlled studies will be needed to establish this. The availability of effective agents with diverse mechanisms of action strongly suggests that major gains in chemotherapy of these tumors will be made in the next decade using combinations of drugs.

Systemic therapy for head and neck squamous cell carcinoma: Historical perspectives and recent breakthroughs

“…In 1962, Espiner and colleagues used intra‐arterial methotrexate for 27 cases of advanced HNSCC; four patients experienced total regression, and partial responses were observed in others. Short follow‐up limited the impact of these findings, and intra‐arterial techniques were also noted to facilitate hemorrhage and embolization; this technique was largely abandoned by the end of the decade . Further trials with systemic methotrexate administration refined dosages and explored strategies to minimize toxicity, such as the use of leucovorin.…”

“…5‐FU and bleomycin were the most studied single‐agent therapies for advanced and recurrent HNSCC in the 1960s. Along with hydroxyurea and cyclophosphamide, these drugs were noted to have response rates in the 30% to 40% range, although durable responses beyond 6 months were rare . Bleomycin demonstrated initial promise because of reduced propensity for myelosuppression, although it did cause significant epithelial toxicity.…”

“…Short follow-up limited the impact of these findings, and intra-arterial techniques were also noted to facilitate hemorrhage and embolization; this technique was largely abandoned by the end of the decade. 4 Further trials with systemic methotrexate administration refined dosages and explored strategies to minimize toxicity, such as the use of leucovorin. The use of methotrexate became more commonplace by the 1970s, particularly in patients with locoregional recurrence and advanced disease.…”

Circulating cycloxygenase-2 in patients with tobacco-related intraoral squamous cell carcinoma and evaluation of its peptide inhibitors as potential antitumor agent

“…The administration of chemotherapy leads to further decline in the general condition of these patients, even though there may be regression of tumor (Bertino et al 1973). Recent evidence suggests that while over expression of COX-2 enhances prostaglandin E2 (PGE2) production and promotes tumor growth, depletion of COX-2 attenuates its growth Wu et al 2004).…”

Current Status of Chemotherapy in the Treatment of Head and Neck Cancer

“…hydroxyurea.1 7 Little efficacy has been noted with any of the corticosteroids, enzymes, or nitrosoureas. 1 In evaluating reports of the efficacy of chemothera¬ peutic agents, it is important to define what constitutes success.…”