Kenneth A. Foon, MD

For decades, initial therapy for chronic lymphocytic leukemia (CLL) consisted of alkylators such as chlorambucil (Leukeran). The introduction of nucleoside analogs such as fludarabine and monoclonal antibodies such as rituximab (Rituxan) markedly changed the initial therapy of CLL, particularly in the United States. Fludarabine and combination regimens such as fludarabine/cyclophosphamide (FC) have achieved higher complete response (CR) rates and progression-free survival (PFS) than chlorambucil in previously untreated CLL, but long-term overall survival has not improved, due to concurrent improvement in salvage therapy of relapsed CLL patients. Upfront chemoimmunotherapy regimens such as fludarabine/rituximab (FR) and fludarabine/cyclophosphamide/rituximab (FCR) have similarly improved CR rates and PFS in previously untreated CLL patients, but it is unclear whether overall survival is improved. Advances in cytogenetic analysis and other biologic prognostic factors have greatly enhanced clinicians' ability to risk-stratify newly diagnosed CLL patients, and knowledge of such prognostic factors is necessary to properly interpret results of clinical treatment studies. The choice of initial therapy for an individual patient should depend upon the patient's age and medical condition, cytogenetic and other prognostic factors, and whether the goal of therapy is maximization of CR and PFS or palliation of symptoms with minimal toxicity.

Head and neck squamous cellcarcinoma (HNSCC) is themost common malignant neoplasmarising in the upper aerodigestivetract, accounting for approximately40,000 new cases each yearin the United States. Despite increasingawareness of the importance ofearly cancer detection, the majorityof patients continue to present withadvanced-stage (stage III/IV) disease.Standard therapy has included surgicalresection followed by externalbeamradiation or chemotherapy inconjunction with radiotherapy(chemoradiation). Although no prospectiveclinical trials have comparedsurgical with nonsurgical therapies,only 50% of patients are cured of theirprimary tumors. Even with successfuleradication of the primary tumor,second primary tumors can be expectedto occur at the rate of 4% to 5% peryear and are often fatal. Given the extrememorbidity and mortality ofHNSCC, new and innovative treatmentsbased on the biologic alterations thatcharacterize these tumors are required.