Sex and adverse events of adjuvant chemotherapy in colon cancer: an analysis of 34,640 patients in the ACCENT database

BACKGROUND: Adjuvant chemotherapy is a standard treatment option for patients with stage III and high-risk stage II colon cancer. Sex is one of several factors responsible for the wide inter-patient variability in drug responses. Amalgamated data on the effect of sex on the toxicity of current standard adjuvant treatment for colorectal cancer are missing. METHODS: The objective of our study was to compare incidence and severity of major toxicities of fluoropyrimidine- (5FU or capecitabine) based adjuvant chemotherapy, with or without oxaliplatin, between male and female patients after curative surgery for colon cancer. Adult patients enrolled in 27 relevant randomized trials included in the ACCENT (Adjuvant Colon Cancer End Points) database, a large, multi-group, international data repository containing individual patient data, were included. Comparisons were conducted using logistic regression models (stratified by study and treatment arm) within each type of adjuvant chemotherapy (5FU, FOLFOX, capecitabine, CAPOX, and FOLFIRI). The following major toxicities were compared (grade III or IV and grade I-IV, according to National Cancer Institute Common Terminology Criteria [NCI-CTC] criteria, regardless of attribution): nausea, vomiting, nausea or vomiting, stomatitis, diarrhea, leukopenia, neutropenia, thrombocytopenia, anemia, and neuropathy (in patients treated with oxaliplatin). RESULTS: Data from 34 640 patients were analyzed. Statistically significant and clinically relevant differences in the occurrence of grade III or IV nonhematological {especially nausea (5FU: odds ratio [OR] = 2.33, 95% confidence interval [CI] = 1.90 to 2.87, P < .001; FOLFOX: OR = 2.34, 95% CI = 1.76 to 3.11, P < .001), vomiting (5FU: OR = 2.38, 95% CI = 1.86 to 3.04, P < .001; FOLFOX: OR = 2.00, 95% CI = 1.50 to 2.66, P < .001; CAPOX: OR = 2.32, 95% CI = 1.55 to 3.46, P < .001), and diarrhea (5FU: OR = 1.35, 95% CI = 1.21 to 1.51, P < .001; FOLFOX: OR = 1.60, 95% CI = 1.35 to 1.90, P < .001; FOLFIRI: OR = 1.57, 95% CI = 1.25 to 1.97, P < .001)} as well as hematological toxicities (neutropenia [5FU: OR = 1.55, 95% CI = 1.37 to 1.76, P < .001; FOLFOX: OR = 1.96, 95% CI = 1.71 to 2.25, P < .001; FOLFIRI: OR = 2.01, 95% CI = 1.66 to 2.43, P < .001; capecitabine: OR = 4.07, 95% CI = 1.84 to 8.99, P < .001] and leukopenia [5FU: OR = 1.74, 95% CI = 1.40 to 2.17, P < .001; FOLFIRI: OR = 1.75, 95% CI = 1.28 to 2.40, P < .001]) were observed, with women being consistently at increased risk. CONCLUSIONS: Our analysis confirms that women with colon cancer receiving adjuvant fluoropyrimidine-based chemotherapy are at increased risk of toxicity. Given the known sex differences in fluoropyrimidine pharmacokinetics, sex-specific dosing of fluoropyrimidines warrants further investigation

Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology

OBJECTIVES: - To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens. METHODS: - The American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Pathology, and American Society of Clinical Oncology convened an expert panel to develop an evidence-based guideline to establish standard molecular biomarker testing and guide therapies for patients with CRC. A comprehensive literature search that included more than 4,000 articles was conducted. RESULTS: - Twenty-one guideline statements were established. CONCLUSIONS: - Evidence supports mutational testing for EGFR signaling pathway genes, since they provide clinically actionable information as negative predictors of benefit to anti-EGFR monoclonal antibody therapies for targeted therapy of CRC. Mutations in several of the biomarkers have clear prognostic value. Laboratory approaches to operationalize CRC molecular testing are presented

Molecular Biomarkers for the Evaluation of Colorectal Cancer

Objectives: To develop evidence-based guideline recommendations through a systematic review of the literature to establish standard molecular biomarker testing of colorectal cancer (CRC) tissues to guide epidermal growth factor receptor (EGFR) therapies and conventional chemotherapy regimens

A community resource for paired genomic and metabolomic data mining

Genomics and metabolomics are widely used to explore specialized metabolite diversity. The Paired Omics Data Platform is a community initiative to systematically document links between metabolome and (meta)genome data, aiding identification of natural product biosynthetic origins and metabolite structures.Peer reviewe

Bethesda handbook of clinical oncology /

Includes bibliographical references and index.Cervical cancer / Posades, Kotz -- Vulvar cancer / Annunziata, Birrer -- Sarcomas and malignancies of the bone / Mansky, Helman -- Skin cancers and melanoma / Hegde, Gause -- Acute leukemias / Craig, Abraham, Monahan -- Chronic leukemias / Quazilbash, Keating -- Chronic myeloid leukemia / Quazilbash, Cortes -- Chronic myeloproliferative diseases / Monga, Devetten -- Multiple myeloma / Neelapu, Dunbar -- Non-Hodgkin's lymphoma / Guitierrez, Little, Wilson -- Hodgkin's lymphoma / Schun, Abraham, Wilson -- Hematopoietic stem cell transplantation / Craig, Abraham, Childs -- AIDS-related malignancies / Kumar, Little -- Carcinoma of unknown primary / Khong -- Central nervous system tumors / Mansky, Duic, Fine -- Endocrine tumors / Menefee, Fojo --Head and neck cancer / Conley ... [et al.] -- Non-small cell lung cancer / Horgan, Breathnach -- Small cell lung cancer / Denduluri, M. Guitierrez -- Esophageal cancer / Leonard, Allegra, Kelsen -- Gastric cancer / Saif -- Biliary tract cancer / Leonard, O'Reilly, Allegra -- Primary cancers of the liver / Leonard, Jarnagin, Allegra -- Colorectal cancer / Kim, Takimoto, Allegra -- Pancreatic cancer / Kim, Gulley, Allegra -- Anal cancer / Saif -- Other gastrointestinal tumors / Saif -- Breast cancer / Mirshahidi, Abraham -- Renal cell cancer / Khong, Klebanoff, Bates -- Prostate cancer / Gulley, Dahut -- Bladder cancer / Agarwal, Dahut -- Testicular carcinoma / Retter, Kramer -- Ovarian cancer / Reed and Altaha -- Endometrial cancer / Annunziata, Birrer --Hematopoietic growth factors / Arlen, Gulley -- Infectious complications in oncology / Wynne, Gea-Banacloche -- General principles of cancer pain management / Messman, Beckrow -- Oncological emergencies and paraneoplastic syndromes / Messman, Siddique -- Psychopharmacological management in the oncology setting / Pao, Rosenstein -- Management of emesis / Kohler -- Nutrition / Dobbin -- End of life care / Carter -- Targeted therapies / Gulley, Curt -- Complementary and alternative medicine in oncology / Mansky, Wallerstedt, Blackman -- Central venous access devices / D. Guiterrez, O'Grady -- Procedures in medical oncology / Demko, Ryan, Loud -- Anticancer agents / Hughes