Alan P. Venook, MD | Authors

The Developing Role of Anti–Epidermal Growth Factor Receptor Agents in the Treatment of Advanced or Metastatic Colorectal Cancer

November 15, 2017

Anti-EGFR therapy is a valuable addition to the armamentarium of treatment options for patients with metastatic colorectal cancer. However, RAS mutation status is an imperfect biomarker for prediction of therapeutic outcomes in this setting. The recent discovery of tumor sidedness as a predictor of response highlights how little we understand about which patients are the most appropriate to receive drugs that target EGFR.

Biomarkers in Colon Cancer: The Chasm Between Expectations and Reality

August 15, 2013

At this juncture, various commercially available assays for colon cancer may be of little added value, and accelerated biomarker development with clinical validation is desperately needed.

Metastatic Colorectal Cancer: A Curable Disease

March 13, 2012

Combined-modality therapy has rendered disease-free an increasing number of patients who were previously considered to be incurable. Still, despite myriad advances in imaging, and in surgical and therapeutic modalities, many patients who undergo resection of limited metastatic disease with curative intent ultimately relapse.

Mutated ras as a Predictor of Response: Is It Ready for the Clinic?

May 15, 2008

Preliminary results from two trials presented at the 44th Annual Meeting of ASCO in Chicago have consolidated the role of K-ras as a biomarker of nonresponse to cetuximab and panitumumab in metastatic colorectal cancer (mCRC). The phase III CRYSTAL and OPUS trials presented unplanned subgroup analyses of the correlation of K-ras status with response to therapy with first-line FOLFIRI or FOLFOX, respectively, with or without cetuximab in patients with mCRC. Both studies demonstrated a clear benefit with the addition of cetuximab in K-ras WT patients.

Emergence of the Epothilones

April 15, 2008

Epothilones, representing a newer class of naturally occurring antimicrotubule macrolides, have emerged as cytotoxic agents with significant antitumor activity against tumors that are resistant to taxanes.

Commentary (Venook): Management of Liver Metastases From Colorectal Cancer

September 01, 2006

The liver is a frequent site of metastatic colorectal disease. Over the past 20 years, improvements in systemic chemotherapy and surgical techniques have improved the survival of patients with hepatic metastases. For 4 decades, fluorouracil and leucovorin were the only drugs available to treat metastatic colorectal cancer, but several new drugs and a variety of novel regimens are now available. Further improvements in results have been seen with the delivery of chemotherapy via the hepatic artery. Surgical resection of liver metastases has been encouraged when possible, and recent advances in surgery such as portal vein embolization, have made liver resection a possibility for more patients. This review considers the timing and sequence of chemotherapy and surgery in this setting, as well as the roles of cryoablation, radiofrequency ablation, and radiation therapy.

Commentary (Venook): Chemotherapy Dosing in the Setting of Liver Dysfunction

July 01, 2005

The dosing of chemotherapy is,at best, an imperfect science.Long-standing convention hasus calculating body surface area totwo decimal places-a largely discreditedand unnecessary exercise-yet wehave so far failed to learn how to incorporatepotentially important variablesrelated to race, sex, and pharmacogenetics.This review, “ChemotherapyDosing in the Setting of Liver Dysfunction,”by Eklund et al highlightsanother limitation in our understandingof how to use chemotherapy: There islittle known about how to dose drugs inpatients with anything other than normalorgan function.

Defining the Role of Hepatic Arterial Infusion Chemotherapy in Metastatic Colorectal Cancer

May 01, 2004

The use of hepatic arterial infusion (HAI) chemotherapy in patientswith liver-only colorectal metastases is based on the pharmacologicprinciple that the regional administration of some drugs can lead tohigher drug concentrations at the site of the metastases and avoid systemictoxicity. Early randomized trials resulted in high response ratesbut did not lead to a survival advantage with HAI. More recent trialshave utilized improved surgical techniques and strict guidelines regardingdose reduction or cessation of HAI chemotherapy, resulting in asignificant reduction in toxicity. In patients with unresectable liver metastases,two recent European trials using HAI fluorouracil (5-FU)again failed to demonstrate an improvement in survival, but both wereplagued by a high complication rate with an associated high proportionof patients failing to receive the assigned treatment. In contrast,the preliminary results of a recent Cancer and Leukemia Group B trialdid demonstrate a survival advantage with HAI floxuridine when comparedto systemically administered 5-FU. Trials investigating the useof HAI chemotherapy in the adjuvant setting have yielded mixed results.Moreover, in light of improved response rates and overall survivalwith newer more active chemotherapeutic and novel agents, theabsolute role of HAI chemotherapy remains undefined.

Regional Strategies for Managing Hepatocellular Carcinoma

March 01, 2000

Since hepatocellular carcinoma almost always develops in patients with underlying hepatitis or cirrhosis of the liver, it cannot be viewed as a single disease. Not only does the biology of the cancer vary depending on the underlying etiology of the liver disease-hepatitis B, hepatitis C, or cirrhosis of another etiology-but also patient outcomes are determined by the interplay between tumor growth and