Riechelmann, Rachel

ASCO Guidelines provide recommendations with comprehensive review and analyses of the relevant literature for each recommendation, following the guideline development process as outlined in the ASCO Guidelines Methodology Manual . ASCO Guidelines follow the ASCO Conflict of Interest Policy for Clinical Practice Guidelines . Clinical Practice Guidelines and other guidance (“Guidance”) provided by ASCO is not a comprehensive or definitive guide to treatment options. It is intended for voluntary use by clinicians and should be used in conjunction with independent professional judgement. Guidance may not be applicable to all patients, interventions, diseases or stages of diseases. Guidance is based on review and analysis of relevant literature and is not intended as a statement of the standard-of-care. ASCO does not endorse third-party drugs, devices, services, or therapies and assumes no responsibility for any harm arising from or related to the use of this information. See complete disclaimer in Appendix 1 and 2 (online only). PURPOSE To provide evidence-based guidance for clinicians who treat patients with stage I-III anal cancer. METHODS A systematic review of the literature conducted by the Minnesota Evidence-based Practice Center provided the evidence base for this guideline. An ASCO Expert Panel reviewed this evidence and came to consensus on a set of evidence-based recommendations. RESULTS The systematic review contained three randomized controlled trials and three nonrandomized studies of interventions that were relevant to the guideline topic and informed the recommendations. RECOMMENDATIONS Mitomycin-C (MMC) with a fluoropyrimidine (fluorouracil [FU] or capecitabine) is recommended as the radiosensitizing component of chemoradiation (CRT) for anal cancer; the Expert Panel recognizes that capecitabine is often used as an orally administered alternative to FU and is currently being used in ongoing clinical trials. Cisplatin with FU is an additional chemotherapy combination that may be recommended as radiosensitizing chemotherapy. Because of the myelosuppression associated with MMC, the preferable regimen for patients with immunosuppression is cisplatin and FU. Cisplatin is not recommended for patients with renal dysfunction, significant neuropathy, or hearing loss, and there is no evidence to recommend substituting carboplatin for cisplatin. Dose and schedule options for recommended chemotherapy agents are included within the full text of the guideline. Routine induction chemotherapy before CRT and additional chemotherapy after CRT are not recommended for patients with localized anal cancer. Additional information is available at www.asco.org/gastrointestinal-cancer-guidelines .

Even though significant improvements in the treatment of colorectal cancer (CRC) have been made in recent years, survival rates for metastatic colorectal cancer (mCRC) are poor. Effective treatment options for metastatic colorectal cancer remain limited, and new therapeutic strategies are desperately needed. Several tyrosine kinase inhibitors (TKIs) and monoclonal antibodies (mAbs) that target angiogenesis, a critical process for facilitating tumor cell growth, invasion, and metastasis, are either approved or in clinical development for the treatment of mCRC. Many of these agents have shown efficacy in mCRC, both as single agents and in combination with standard chemotherapy regimens. However, there is a need for predictive markers of response to identify those patients most likely to benefit from antiangiogenic therapy, and, to date, no markers of this type have been validated in patients. Additionally, because antiangiogenic agents typically cause cytostatic as opposed to cytotoxic antitumor effects, it is important to determine the best strategies for evaluating therapeutic response in mCRC to ensure maximum clinical benefit. In this review, we summarize the efficacy and tolerability of approved and investigational antiangiogenic agents for the treatment of mCRC. We also discuss potential markers of response to antiangiogenic agents and how these markers, along with appropriate endpoint selection, can improve clinical trial design.