ABSTRACT
The NCCN Guidelines for Rectal Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Rectal Cancer Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize major discussion points from the 2015 NCCN Rectal Cancer Panel meeting. Major discussion topics this year were perioperative therapy options and surveillance for patients with stage I through III disease.
Subject(s)
Rectal Neoplasms/therapy , Combined Modality Therapy , Humans , Practice Guidelines as Topic , Rectal Neoplasms/diagnosisABSTRACT
The NCCN Guidelines for Colon Cancer address diagnosis, pathologic staging, surgical management, perioperative treatment, posttreatment surveillance, management of recurrent and metastatic disease,and survivorship. This portion of the guidelines focuses on the use of systemic therapy in metastatic disease. The management of metastatic colorectal cancer involves a continuum of care in which patients are exposed sequentially to a variety of active agents, either in combinations or as single agents. Choice of therapy is based on the goals of treatment, the type and timing of prior therapy, the different efficacy and toxicity profiles of the drugs, the mutational status of the tumor, and patient preference.
Subject(s)
Antineoplastic Agents/therapeutic use , Colonic Neoplasms/drug therapy , Colonic Neoplasms/surgery , Liver Neoplasms/secondary , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab , Camptothecin/adverse effects , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Capecitabine , Cetuximab , Colonic Neoplasms/pathology , Deoxycytidine/adverse effects , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Disease Progression , Fluorouracil/adverse effects , Fluorouracil/analogs & derivatives , Fluorouracil/therapeutic use , GTP Phosphohydrolases/genetics , Humans , Leucovorin/adverse effects , Leucovorin/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/surgery , Membrane Proteins/genetics , Organoplatinum Compounds/adverse effects , Organoplatinum Compounds/therapeutic use , Oxaloacetates , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras) , Treatment Outcome , ras Proteins/geneticsABSTRACT
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions surrounding metastatic colorectal cancer for the 2013 update of the guidelines. Importantly, changes were made to the continuum of care for patients with advanced or metastatic disease, including new drugs and an additional line of therapy.
Subject(s)
Colonic Neoplasms/therapy , Medical Oncology/standards , Colonic Neoplasms/pathology , Humans , Medical Oncology/education , Neoplasm Metastasis , Practice Guidelines as TopicABSTRACT
The NCCN Clinical Practice Guidelines in Oncology for Colon Cancer begin with the clinical presentation of the patient to the primary care physician or gastroenterologist and address diagnosis, pathologic staging, surgical management, perioperative treatment, patient surveillance, management of recurrent and metastatic disease, and survivorship. The NCCN Colon Cancer Panel meets annually to review comments from reviewers within their institutions and to reevaluate and update their recommendations. In addition, the panel has interim conferences as new data necessitate. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel's discussions regarding the treatment of localized disease for the 2013 update of the guidelines.
Subject(s)
Colonic Neoplasms/diagnosis , Colonic Neoplasms/therapy , Early Detection of Cancer , Humans , Neoadjuvant Therapy , Neoplasm StagingABSTRACT
These NCCN Clinical Practice Guidelines in Oncology provide recommendations for the management of rectal cancer, beginning with the clinical presentation of the patient to the primary care physician or gastroenterologist through diagnosis, pathologic staging, neoadjuvant treatment, surgical management, adjuvant treatment, surveillance, management of recurrent and metastatic disease, and survivorship. This discussion focuses on localized disease. The NCCN Rectal Cancer Panel believes that a multidisciplinary approach, including representation from gastroenterology, medical oncology, surgical oncology, radiation oncology, and radiology, is necessary for treating patients with rectal cancer.
Subject(s)
Rectal Neoplasms/drug therapy , Rectal Neoplasms/radiotherapy , Rectal Neoplasms/surgery , Combined Modality Therapy , Genetic Predisposition to Disease , Guidelines as Topic , Humans , Neoplasm Staging , Rectal Neoplasms/genetics , Rectal Neoplasms/pathology , Risk Assessment , Vitamin D/metabolismABSTRACT
The workup and management of squamous cell anal carcinoma, which represents the most common histologic form of the disease, are addressed in the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Anal Carcinoma. These NCCN Guidelines Insights provide a summary of major discussion points of the 2012 NCCN Anal Carcinoma Panel meeting. In summary, the panel made 4 significant changes to the 2012 NCCN Guidelines for Anal Carcinoma: 1) local radiation therapy was added as an option for the treatment of patients with metastatic disease; 2) multifield technique is now preferred over anteroposterior-posteroanterior (AP-PA) technique for radiation delivery and the AP-PA technique is no longer recommended as the standard of care; 3) PET/CT should now be considered for radiation therapy planning; and 4) a section on risk reduction was added to the discussion section. In addition, the panel discussed the use of PET/CT for the workup of anal canal cancer and decided to maintain the recommendation that it can be considered in this setting. They also discussed the use of PET/CT for the workup of anal margin cancer and for the assessment of treatment response. They reaffirmed their recommendation that PET/CT is not appropriate in these settings.
Subject(s)
Anus Neoplasms/radiotherapy , Carcinoma, Squamous Cell/radiotherapy , Anus Neoplasms/diagnosis , Anus Neoplasms/diagnostic imaging , Carcinoma, Squamous Cell/diagnosis , Carcinoma, Squamous Cell/diagnostic imaging , Humans , Multimodal Imaging , Positron-Emission Tomography , Tomography, X-Ray ComputedABSTRACT
PURPOSE: To determine whether floxuridine (FUDR) can be delivered with low hepatic toxicity through the portal vein (PV) as an adjuvant to surgically treated colorectal metastases. PATIENTS AND METHODS: Fifty-one patients undergoing complete resection and/or ablation for colorectal hepatic metastases were prospectively enrolled at a National Cancer Institute-designated comprehensive cancer center. Two sequential phase II trials were performed. Each trial included complete surgical treatment followed by sequential, alternating (22 patients) or concurrent (29 patients) regional PV FUDR and systemic fluorouracil (FU) with leucovorin chemotherapy. RESULTS: Fifty percent of patients were male. The mean age at diagnosis was 57 years. The mean number of lesions resected was three (range, one to 11 lesions). The stage at diagnosis was II, III, and IV in 16.9%, 52.8%, and 28.3% of patients, respectively. One- and 3-year overall survival rates were 92.7% and 41.8%, respectively. The 1- and 3-year disease-free survival rates were 64.5% and 19%, respectively. The site of first recurrence was hepatic in 35.9% of patients. Treatment was terminated early in 24 patients (17 patients progressed, two refused treatment, and five had nonhepatic toxicities). Fifty-five percent of patients received 75% to 100% of the planned FUDR courses, and 72% received greater than 50% of the planned FUDR dose. Only four patients required dose reductions of FUDR because of grade 3 hepatic toxicity. No patient required biliary stenting or had discontinuation of PV infusion because of hepatic toxicity. CONCLUSION: The delivery of PV FUDR and FU with leucovorin can be performed with a high percentage of expected drug delivery and a low drug-induced hepatic toxicity rate, while achieving acceptable overall and disease-free survival.
Subject(s)
Antimetabolites, Antineoplastic/adverse effects , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Floxuridine/adverse effects , Floxuridine/therapeutic use , Liver Neoplasms/drug therapy , Liver Neoplasms/secondary , Adult , Aged , Antimetabolites, Antineoplastic/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Chemotherapy, Adjuvant , Disease-Free Survival , Female , Floxuridine/administration & dosage , Fluorouracil/administration & dosage , Humans , Infusions, Intravenous , Leucovorin/administration & dosage , Liver Neoplasms/surgery , Male , Middle Aged , Portal VeinSubject(s)
Carcinoma/therapy , Colonic Neoplasms/therapy , Practice Guidelines as Topic , Algorithms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma/diagnosis , Carcinoma/etiology , Carcinoma/pathology , Colonic Neoplasms/diagnosis , Colonic Neoplasms/etiology , Colonic Neoplasms/pathology , Combined Modality Therapy , Continuity of Patient Care , Digestive System Surgical Procedures/statistics & numerical data , Humans , Maintenance Chemotherapy/methods , Maintenance Chemotherapy/statistics & numerical data , Medical Oncology/legislation & jurisprudence , Medical Oncology/standards , Neoadjuvant Therapy , Neoplasm Metastasis , Radiotherapy/statistics & numerical data , RecurrenceABSTRACT
BACKGROUND: GTI-2040 is a 20-mer antisense oligonucleotide targeting the mRNA of ribonucleotide reductase M2. It was combined with oxaliplatin and capecitabine in a phase I trial in patients with advance solid tumors based on previous studies demonstrating potentiation of chemotherapy with ribonucleotide reductase inhibitors. METHODS: Patients at least 18 years of age with advanced incurable solid tumors and normal organ function as well as a Karnofsky performance status of > or =60% were eligible. One prior chemotherapy regimen for advanced disease or relapse within 12 months of adjuvant chemotherapy was required. Patients could have received prior fluoropyrimidines, including capecitabine, but not oxaliplatin. Treatment cycles were 21 days. In each cycle, GTI-2040 was given as a continuous intravenous infusion over 14 days, oxaliplatin as a 2-h intravenous infusion on day 1, and capecitabine orally twice a day for 14 days. In cycle 1 only, oxaliplatin and capecitabine were started on day 2 to allow ribonucleotide reductase mRNA levels to be measured with and without oxaliplatin and capecitabine. Doses were escalated in cohorts of three patients using a standard 3 + 3 design until the maximum tolerated dose was established, defined as no more than one first-cycle dose-limiting toxicity among six patients treated at a given dose level. RESULTS: The maximum tolerated dose was estimated to be the combination of GTI-2040 3 mg/kg per day for 14 days, capecitabine 600 mg/m(2) twice daily for 14 days, and oxaliplatin 100 mg/m(2) every 21 days. Dose-limiting toxicities were hematologic. GTI-2040 pharmacokinetics, obtained at steady-state on days 7 and 14, showed the high inter-patient variability previously reported. Two of six patients had stable disease at the maximum tolerated dose and one patient, with heavily pre-treated non-small cell lung cancer, had a partial response at a higher dose level. In samples from a limited number of patients, there was no clear decrease in ribonucleotide reductase expression in peripheral blood mononuclear cells during treatment. CONCLUSION: A combination of GTI-2040, capecitabine and oxaliplatin is feasible in patients with advanced solid tumors.
Subject(s)
Deoxycytidine/analogs & derivatives , Fluorouracil/analogs & derivatives , Neoplasms/drug therapy , Oligodeoxyribonucleotides/therapeutic use , Organoplatinum Compounds/therapeutic use , Adult , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/pharmacokinetics , Antineoplastic Agents/therapeutic use , Capecitabine , Deoxycytidine/administration & dosage , Deoxycytidine/adverse effects , Deoxycytidine/therapeutic use , Drug Therapy, Combination , Female , Fluorouracil/administration & dosage , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Gene Expression/drug effects , Gene Expression/genetics , Humans , Leukocytes, Mononuclear/drug effects , Leukocytes, Mononuclear/metabolism , Male , Maximum Tolerated Dose , Middle Aged , Neoplasm Metastasis/drug therapy , Oligodeoxyribonucleotides/administration & dosage , Oligodeoxyribonucleotides/adverse effects , Oligodeoxyribonucleotides/pharmacokinetics , Organoplatinum Compounds/administration & dosage , Organoplatinum Compounds/adverse effects , Oxaliplatin , Ribonucleoside Diphosphate Reductase/antagonists & inhibitors , Ribonucleoside Diphosphate Reductase/genetics , Treatment Outcome , Tumor Suppressor Proteins/geneticsABSTRACT
PURPOSE: Prolonged survival for patients with unresectable hepatocellular carcinoma (HCC) is consistently reported at lower than 6 months. Oxaliplatin has recently demonstrated activity in HCC. The objective of this study was to determine the response rate, survival, time to progression, and toxicity in patients with poor prognosis HCC when treated with oxaliplatin. EXPERIMENTAL DESIGN: Patients were required to have measurable recurrent, metastatic or unresectable HCC, and to have previously been exposed to no more than 2 prior chemotherapy regimens. Karnofsky performance of 70% or above and adequate organ and hematologic function were required. All patients received treatment with oxaliplatin 100 mg/m on day 1 and 15 as a 2-hour intravenous infusion and were pretreated with antiemetics. Treatment was repeated every 28 days. RESULTS: Thirty-six patients were enrolled and evaluated, although 6 expired before the first planned evaluation. Karnofsky performance status was 70/80/90/100% in 5/9/9/13 patients, respectively. The median time to progression was 2 months; median survival was 6 months. The 6-month overall survival was 55% (95% confidence interval 41%-74%), and the 6 month event-free survival was 11% (95% confidence interval 4%-28%). CONCLUSION: Single agent, oxaliplatin, has produced one partial response of good duration in 36 patients, but failed to meet the a priori criterion for promise in this trial. Sixteen patients were observed to have stable disease with a well tolerated toxicity profile. The combination of oxaliplatin and other agents should be considered to treat HCC in those patients with good functional status.
Subject(s)
Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Organoplatinum Compounds/therapeutic use , Salvage Therapy , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/secondary , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/secondary , Cholangiocarcinoma/drug therapy , Cholangiocarcinoma/secondary , Female , Humans , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Oxaliplatin , Prognosis , Survival Rate , Treatment OutcomeABSTRACT
The past decade has seen a significant survival improvement for patients with metastatic colorectal cancer, fueled in large part by the arrival of active novel chemotherapeutic drugs and their incorporation into combination regimens. Several randomized trials have successfully integrated oxaliplatin and irinotecan into previously existing 5-fluorouracil (5-FU)-based regimens for advanced colorectal cancer, resulting in median survivals that have risen from 9 months to almost 2 years. Even as the ideal combinations and sequences of these regimens are elucidated, targeted therapies such as recently approved bevacizumab and cetuximab have been added to treatment protocols, with favorable consequences. We review the evolution of primary chemotherapy for advanced colorectal cancer, focusing on the trials that have led to the new standard first-line treatments. We also review the data on newer targeted therapies, especially in combination with cytotoxic therapy.
Subject(s)
Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/secondary , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antimetabolites, Antineoplastic/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Capecitabine , Cetuximab , Deoxycytidine/analogs & derivatives , Deoxycytidine/therapeutic use , Fluorouracil/therapeutic use , Humans , Irinotecan , Leucovorin/therapeutic use , Organoplatinum Compounds/therapeutic use , OxaliplatinABSTRACT
We evaluated the antitumor activity of tandem cycles of high-dose chemotherapy with autologous peripheral stem cell transplantation (aPSCT) in relapsed germ cell tumors by using high-dose paclitaxel, carboplatin, etoposide, and ifosfamide. Thirty-three patients were entered, and 31 underwent protocol therapy. Paclitaxel 350 mg/m2 (5 patients) or 425 mg/m2 (26 patients) by 24-hour continuous intravenous infusion was followed by 3 daily doses of carboplatin and either etoposide (cycle 1) or ifosfamide/mesna (cycle 2). The carboplatin dose had a calculated area under the curve of 7 mg-min/mL, and the daily dose of etoposide was 20 mg/kg (cycle 1). Ifosfamide 3 g/m2/d for 3 days (with mesna uroprotection) was substituted for etoposide in cycle 2. Each cycle was supported by granulocyte colony-stimulating factor-mobilized peripheral blood stem cells. Thirty-one patients were evaluable for response, toxicity, and long-term disease control. Two patients did not undergo aPSCT because of rapid disease progression. Nineteen patients received both cycles of aPSCT, 8 progressed after cycle 1, 3 refused the second cycle, and 1 died of fungal infection during cycle 1. Twelve patients remain relapse free at a median of 67 months from the initiation of therapy. Whereas the International Germ Cell Cancer Collaborative Group category at the time of initial diagnosis did not seem to predict outcome, the patient's probability of achieving durable remission was significantly associated with the Beyer prognostic score at the time of protocol entry. Regimens containing the most active agents in relapsed nonseminomatous germ cell tumors, including high-dose paclitaxel, are well tolerated and have promising activity even in patients with poor-risk features who do not achieve durable remissions with standard therapy. The Beyer prognostic system is a valuable predictor for patients undergoing aPSCT.