Adjuvant Colorectal Cancer Research Articles

First line chemotherapy with FOLFOX 4 in elderly patients (>65 years) with advanced or metastatic gastric cancer (A/MGC): A pilot study

14095 Background: Cisplatin/5-FU based regimens are considered therapies of choice for the treatment of A/MGC even if severe toxicities are reported especially in elderly pts. FOLFOX 4 regimen is standard chemotherapy in adjuvant and metastatic colorectal cancer and it is effective and well tolerated also in elderly population. Several trials have showed activity and safety of FOLFOX regimen in A/MGC. For these reasons, we carried out this pilot study in order to evaluate the feasibility of FOLFOX 4 in elderly pts (>65 yrs) with A/MGC. Methods: From June 2003 to June 2005 we treated with FOLFOX 4 regimen 31 pts with median age of 70 yrs (range 66–79), 20 males and 11 females, ECOG PS 0–2 with MGC in 19 cases and AGC in 12 cases. All pts had measurable disease according to RECIST criteria, NCI-CTC was employed to grade toxicity except for neurotoxicity graded by specific scale. Results: We recorded 4 CR (13%), 6 PR (19%), 9 SD (29%) and 12 PD for an ORR 32% and median TTP of 6.8 months. A total of 281 courses were delivered with a median of 8 courses (range 4–15) per pt. No toxic deaths occurred and no therapy has been ended for toxicity or pt refusal. Pts did not receive G-CSF support. 43 courses were delayed for toxicity (maximum 2 weeks). Haematological adverse events were: 23 episodes of neutropenia G1/2, 8 episodes of G3 and 3 episodes of G4 neutropenia; G1/2 thrombocytopenia occurred in 15 episodes; anemia G1/2 was reported in 13 episodes. Besides, we recorded 12 episodes of emesis G2 and 2 episodes of G3; 24 episodes of G1/2 and 7 episodes of G3 oral mucositis were recorded; diarrhoea G1/2 was a common event (around 50% of cycles) while severe diarrhoea was a rare. Alopecia G1/2 was registered in 19 pts, G1neurosensorial toxicity (specific scale) occurred in 16 pts, G2 in 7 pts and G3 in one pt. One pt had hypersensitivity reaction at first infusion that did not occurred anyone by prolonged infusion of L-OHP. Conclusions: Our data show that FOLFOX 4 is active in the treatment of A/MGC and that toxicity profile is favourable in elderly population in comparison to standard regimens. No significant financial relationships to disclose.

Enrolment in the AVANT trial in patients with post-surgical adjuvant colorectal cancer has been temporarily halted over a safety concern

Enrolment in the AVANT trial in patients with post-surgical adjuvant colorectal cancer has been temporarily halted over a safety concern

Enrolment in the AVANT trial in patients with post-surgical adjuvant colorectal cancer has been temporarily halted over a safety concern

Enrolment in the AVANT trial in patients with post-surgical adjuvant colorectal cancer has been temporarily halted over a safety concern

Rapid Evolution in Colorectal Cancer: Therapy Now and Over the Next Five Years

A large number of patients with colorectal cancer have relatively early disease, and thus, adjuvant therapy has the potential to save lives. In stage III patients, there has been a steady improvement in 3-year disease-free survival with the use of 5-fluorouracil/leucovorin (5-FU/LV) regimens and capecitabine (Xeloda); Hoffmann-La Roche Inc., Nutley, NJ, http://www.rocheusa.com) regimens. A median survival longer than 20 months was observed in patients with metastatic disease when treated with combination chemotherapy containing oxaliplatin (Eloxatin); Sanofi-Synthelabo Inc., New York, http://www.sanofi-synthelabo.us) or irinotecan (Camptosar); Pfizer Pharmaceuticals, New York, http://www.pfizer.com). This has led to 5-FU/LV/oxaliplatin becoming standard therapy, along with 5-FU/LV/irinotecan. New data confirm the beneficial effect on disease-free survival of adding oxaliplatin to adjuvant colorectal cancer regimens based on 5-FU. These regimens show an effect when given in bolus as well as in infusional schedules. Interest in future adjuvant regimens focuses on the potential additional benefit of molecularly targeted agents, such as bevacizumab (Avastin); Genentech, Inc., South San Francisco, CA, http://www.gene.com), and on the ability of applied genomics to distinguish between high- and low-risk populations.

Stage II Colorectal Cancer: To Treat or not to Treat

The Oncologist 2005;10:332–334 www.TheOncologist.com Correspondence: Patrick G. Johnston, M.D., Ph.D., FRCP, FRCPI, Department of Oncology, Queen’s University Belfast, University Floor, Belfast City Hospital, Belfast BT9 7AB, Northern Ireland. Telephone: 44-28-90-263911; Fax: 44-28-90263744; e-mail: oncology@qub.ac.uk Received March 8, 2005; accepted for publication March 18, 2005. ©AlphaMed Press 1083-7159/2005/$12/00/0 INTRODUCTION Colorectal cancer (CRC) accounts for 10%–15% of all cancers and is the leading cause of cancer deaths in the Western world. Up to 40%–50% of patients who undergo potentially curative surgery alone ultimately relapse and die of metastatic disease [1]. The most important prognostic indicator for survival in colon cancer is tumor stage, which is determined by the depth of penetration through the bowel wall and the number of lymph nodes involved. Over the last 15 years, the development of adjuvant chemotherapy given after surgical removal of tumors for patients with stage II and stage III disease has been used to reduce the risk of recurrence of cancer that may result from remaining tumor cells not detectable after surgery. Many thousands of patients with CRC have been included in clinical trials to assess the potential benefit of various combinations of chemotherapeutic agents. Since the National Institutes of Health 1990 consensus conference, the administration of adjuvant 5-fluorouracil (FU)–based therapy for all medical patients with stage III colorectal cancer has become standard of care and has resulted in a 30%–40% decrease in relapse and mortality rates versus treatment with surgery alone [2]. At the time, the panel did not recommend adjuvant therapy for stage II CRC patients outside the realm of clinical trials, as the data at that time did not support adjuvant therapy for stage II disease. However, one of the problems in the analysis of stage II disease has been the requirement for very large numbers of patients due to the overall favorable prognosis for this subgroup of patients. In adjuvant CRC studies, most clinical trials have included patients with both stage II and stage III disease, and most of those trials have been insufficiently powered to detect any treatment benefit in stage II patients. In stage II CRC, there is tumor penetration through the bowel wall involving the serosa; however, there is no involvement of regional lymph nodes or distant metastases. While the overall survival in this subgroup of patients is approximately 70%–80% 5 years after surgery, in high-risk stage II disease, the clinical outcome is similar to that of patients with stage III disease. Currently, these high-risk patients are identified by tumors that not only penetrate the bowel wall but also show evidence of adhesion to or invasion of surrounding structures, free perforation, obstruction, or aneuploidy. More importantly, recent data, using molecular markers such as loss of heterozygosity (LOH) of 18q or the presence of microsatellite stable tumors, have helped to identify a subgroup of patients with both stage II and stage III CRC who may have much worse prognoses and in whom the administration of chemotherapy may be beneficial

Sixty-day all-cause mortality rates in patients treated for gastrointestinal cancers, in randomised trials, at the Royal Marsden Hospital

The aim of this study was to determine the 60-day all-cause mortality rate, during chemotherapy, for patients with oesophagogastric, pancreatic, and colorectal cancer. We analysed 1720 patients that were treated within randomised trials. The minimum follow-up period was >60 days. Sixty-day mortality and 95% Confidence Intervals (CI) were calculated from the Kaplan–Meier survival curves. Causes of death were classified as treatment-related, disease-related or vascular syndrome-induced deaths. Patients with oesophagogastric cancer that could not tolerate a cis-platinum-containing regimens were treated with infused 5-fluorouracil (5FU) ± mitomycin-C (MMC). The 60-day mortality rate depends upon the site of the primary tumour and the disease status (adjuvant versus advanced). The rate of treatment- and vascular syndrome-induced deaths was ⩽1.8%. For patients with advanced disease, most of the early deaths were disease-related. In adjuvant colorectal cancer, one patient died within 60 days (myocardial infarction). This study provides a benchmark for assessing the safety of regimens used in these disease settings.

Novel approaches to selective treatments of human solid tumors: Laboratory and clinical correlation: International symposioum held at the Rosewell Park Cnacer Institute, Buffalo, N.Y, U.S.A., Sept. 1992 (organized by Dr.Y.M. Rustum)

Proceedings of an international symposium held in Buffalo, N.Y., September 1992. With the major diseases of focus being advanced and adjuvant colorectal cancer, head and neck cancer, and breast cancers, the volume is divided into sections devoted to fluoropyrimidine metabolism and mechanism of actio

Late Effects of Low-Dose Adjuvant Chemotherapy in Colorectal Cancer

As part of a systematic program to evaluate the late effects of antineoplastic therapy in randomized clinical trials, patients enrolled in the low-dose thio-TEPA (TSPA) and 5-fluoro-2'-deoxyuridine (FdUrd) adjuvant colorectal cancer protocols of the Veterans Administration (VA) Surgical Oncology Group between 1958 and 1964 were studied. All patients received surgery with curative intent; 470 also received TSPA, 176 received FdUrd, and 867 received surgery only. The unique VA system permitted complete follow-up through 1977, with 10,902 person-years of observation accrued among 1,613 male patients (mean survival = 6.8 yr). Expected mortality and cancer incidence were computed by applying U.S. Mortality Statistics and Connecticut Tumor Registry age-, race-, sex-, and calendar time-specific rates to the person-years of observation. The mortality experience of the 3 groups was similar. Overall, there was a significant excess in total mortality (observed/expected = 1,359/553) attributable mainly to colorectal cancer (584/14), arteriosclerotic heart disease (258/215.9), pneumonia (41/17), gastric and duodenal ulcers (15/4), and cirrhosis (14/6). No excess mortality from noncolorectal cancers was apparent, nor were there significant differences by treatment: TSPA (22/22), FdUrd (9/12), and surgery only (50/42). Among 1,402 white patients, no significant excess of incident noncolorectal cancers were observed among patients treated with TSPA (30/31, FdUrd (14/15), or surgery only (63/58). Seven incident cases of leukemia developed (4.1 expected) among all patients of various groups: TSPA (3/1.3), FdUrd (1/0.6), and surgery only (3/2.2). No excess of new primary cancers was observed among 211 nonwhite patients. An inverse relationship between the occurrence of second primary cancer and age at diagnosis, irrespective of therapy, was suggested. The results demonstrated the feasibility of this approach for assessment of late complications of anticancer therapy and suggested no measurable carcinogenic effect following very low doses of TSPA and FdUrd in a population of this size.