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Chemotherapy as a Single Modality

  • Chemotherapy has come to be recognized as a vital part of treatment of the locally advanced head and neck cancer patient. The goals of chemotherapy are outlined in Table 46-1.

    • What had been clear since the 1970s were the high rates of response to induction chemotherapy with single agents such as methotrexate, bleomycin, cisplatin, and 5-fluorouracil (5-FU).

  • Table 46-2 lists the most commonly used chemotherapeutic and biologic agents for head and neck cancer.

  • In the 1980s, with the introduction of the combination of cisplatin and 5-FU, rates of complete remission approached 25%, while overall response rates approached 45%. Treatment was always followed by definitive local therapy with either radiation therapy or surgery as responses were always thought to be transient. The combination was also noted to be effective in the treatment of distant metastatic disease.

  • The cisplatin/5-FU combination soon became established as the standard regimen for the treatment of locally advanced and metastatic head and neck squamous cell carcinomas. However, for patients with previously treated disease, the rate of response to systemic chemotherapy was substantially diminished to disappointing rates of 5% to 15%. Nonetheless, this dramatic sensitivity to chemotherapy in previously untreated disease suggested that this treatment modality might decrease distant metastatic disease, improve locoregional control, permit organ preservation, and boost overall survival.

  • A number of trials were conducted during the 1970s and 1980s to test adjuvant chemotherapy for head and neck cancer. Meta-analysis showed an insignificant overall improvement in cancer mortality of 0.5%. Neither single agent nor combination chemotherapy produced a significant reduction of cancer deaths. The mortality rate from chemotherapy in nine series averaged 6.5%. These disappointing results have led to the abandonment of adjuvant chemotherapy following definitive treatment for locally advanced head and neck squamous cell carcinomas, with the prominent exception of the nasopharyngeal subsite.

Table 46-1Potential Goals of Chemotherapy
Table 46-2Commonly Used Chemotherapeutic and Biological Agents in Head and Neck Cancer

Chemotherapy Combined With Radiation Therapy

  • The goal of concurrent chemotherapy with radiation is to increase locoregional control and prevent distant metastases. A number of single agents have been studied since the late 1960s, including bleomycin, methotrexate, hydroxyurea, mitomycin-C, 5-FU, and cisplatin.

  • Most studies failed to report an improvement in overall survival, although a number of agents conferred an increased response rate to radiation therapy. Chemotherapy also was complicated by systemic toxicity from the agent used. Methotrexate conferred significant mucosal and cutaneous toxicity, ...

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