Chemotherapy of Recurrent HNSCC - Head and neck cancer

Clinical testing of new cytotoxic agents traditionally has been conducted first in patients with recurrent disease, followed by testing in combined modality treatments in patients with potentially curable disease. The majority of patients included in the following discussion has recurrent disease and constitute the principal study group; a minority have metastatic or advanced unresectable disease. We refer to this patient group generically as "recurrent," although many studies discussed under this rubric include the minority cases also.

Chemotherapy has had no impact on overall survival in recurrent HNSCC. The purely clinical noninvestigational goal of chemotherapy in recurrent disease has been to achieve palliation, unlike the goal of primary chemotherapy trials, which is to cure locally advanced untreated cancer. The overall prognosis in recurrent HNSCC is dismal (median survival of 4 to 6 months).

Lumped diagnostically under HNSCC is a diverse group of cancers with markedly variable natural histories (fully discussed in the "Biology" section above) and, therefore, markedly variable responses to chemotherapy. Important diversities also occur in HNSCC relapse patterns, that is, at the primary site, in regional nodes, and at distant sites after definitive local therapy. These and many other diversities make it extremely difficult to interpret results of chemotherapy trials in cancers of this region.

Many chemotherapy studies encompass all guises of recurrent HNSCC. They run the gamut from minimal, resectable disease seen locally after radiation therapy to bulky regional and distant disease occurring after surgery, radiotherapy, and even primary and/or salvage chemotherapy. Often these last salvage patients are excluded from further chemotherapy trials because of their extremely poor prognosis. Other poor-risk patients, such as those with unresectable disease resistant to neoadjuvant chemotherapy or with short disease-free intervals or persistent disease after primary therapy, are included in many trials. Although patients with advanced resectable disease should be included in trials of primary therapy, the varying definition of resectable among different head and neck surgeons can place these patients in "recurrent" trials.

Single-Agent Trials
Response rates of different trials with the same agent have varied markedly due to HNSCC's great heterogeneity and because of differences in trial designs. Pooled results indicate that eight drugs show single-agent response rates of 15% or higher and remission durations of 3 to 5 months (Table 90-26). The five longest-studied of these agents are methotrexate, cisplatin, bleomycin, 5-FU, and carboplatin. The three newer agents in this group are paclitaxel, docetaxel, and ifosfamide.

Methotrexate, according to many oncologists, is the standard palliative therapy for recurrent or metastatic HNSCC. The standard dose and schedule for palliation are 40 mg/m/wk intravenously or intramuscularly, with dose escalations to 60 mg/m/wk until mild toxicity or any tumor response is achieved. This methotrexate dose and schedule are relatively nontoxic, inexpensive, and convenient, features that are critical to palliative therapy.