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Latest Article

Managing CLL: A New Level of Sophistication

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.

Latest Article

Current Status of Adjuvant Therapy for Colorectal Cancer

Adjuvant therapy with chemotherapy and/or radiation therapy inaddition to surgery improves outcome for patients with high-risk carcinomasof the colon or rectum. For colon cancer, fluorouracil (5-FU)combined with leucovorin is a current standard of care that improveslong-term survival. A recent European trial (MOSAIC) has documentedsignificant improvement in 3-year disease-free survival when oxaliplatin(Eloxatin) was added to infusional 5-FU and leucovorin in the FOLFOXregimen. Two US cooperative group trials will evaluate the addition ofantiangiogenesis therapy with bevacizumab (Avastin) to chemotherapy.A third trial will evaluate FOLFOX, irinotecan (Camptosar) combinedwith infusional 5-FU and leucovorin (FOLFIRI), and the sequentialuse of FOLFOX followed by FOLFIRI. In rectal cancer, postoperative5-FU–based chemotherapy combined with irradiation can improve bothlocal tumor control and survival. The German Rectal Cancer Grouphas recently reported that preoperative combined-modality therapy isless toxic and more effective in preventing local tumor relapse comparedto similar treatment given postoperatively. A coordinated pair ofcooperative group clinical trials will evaluate oral capecitabine (Xeloda)as a radiation enhancer in the preoperative setting, and the FOLFOXand FOLFIRI regimens compared to 5-FU and leucovorin followingsurgery. Predictive and prognostic molecular markers will be studiedin these new adjuvant therapy clinical trials for both colon and rectalcancer with the goal of developing future regimens tailored to individualpatients. There has been a recent and dramatic increase in thepace of drug development for colorectal cancer which holds promise tofurther improve curative therapy as part of a multidisciplinary approachin the surgical adjuvant setting.