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John S Macdonald

Publications and source records attributed to John S Macdonald.

At least 19 recordsLinked to original sources
PubMed2006

ASCO 2006 update of recommendations for the use of tumor markers in gastrointestinal cancer.

PURPOSE: To update the recommendations for the use of tumor marker tests in the prevention, screening, treatment, and surveillance of gastrointestinal cancers. METHODS: For the 2006 update, an update committee composed of members from the full Panel was formed to complete the review and analysis of data published since 1999. Computerized literature searches of Medline and the Cochrane Collaboration Library were performed. The Update Committee's literature review focused attention on available systematic reviews and meta-analyses of published tumor marker studies. RECOMMENDATIONS AND CONCLUSION: For colorectal cancer, it is recommended that carcinoembryonic antigen (CEA) be ordered preoperatively, if it would assist in staging and surgical planning. Postoperative CEA levels should be performed every 3 months for stage II and III disease for at least 3 years if the patient is a potential candidate for surgery or chemotherapy of metastatic disease. CEA is the marker of choice for monitoring the response of metastatic disease to systemic therapy. Data are insufficient to recommend the routine use of p53, ras, thymidine synthase, dihydropyrimidine dehydrogenase, thymidine phosphorylase, microsatellite instability, 18q loss of heterozygosity, or deleted in colon cancer (DCC) protein in the management of patients with colorectal cancer. For pancreatic cancer, CA 19-9 can be measured every 1 to 3 months for patients with locally advanced or metastatic disease receiving active therapy. Elevations in serial CA 19-9 determinations suggest progressive disease but confirmation with other studies should be sought. New markers and new evidence to support the use of the currently reviewed markers will be evaluated in future updates of these guidelines.

Biomarkers, Tumor↗
PubMed2006

Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144.

PURPOSE: Adjuvant chemoradiotherapy after or before resection of high-risk rectal cancer improves overall survival (OS) and pelvic control. We studied three postoperative fluorouracil (FU) radiochemotherapy regimens. PATIENTS AND METHODS: After resection of T3-4, N0, M0 or T1-4, N1, 2M0 rectal adenocarcinoma, 1,917 patients were randomly assigned to arm 1, with bolus FU in two 5-day cycles every 28 days before and after radiotherapy (XRT) plus FU via protracted venous infusion (PVI) 225 mg/m2/d during XRT; arm 2 (PVI-only arm), with PVI 42 days before and 56 days after XRT + PVI; or arm 3 (bolus-only arm), with bolus FU + leucovorin (LV) in two 5-day cycles before and after XRT, plus bolus FU + LV (levamisole was administered each cycle before and after XRT). Patients were stratified by operation type, T and N stage, and time from surgery. RESULTS: Median follow-up was 5.7 years. Lethal toxicity was less than 1%, with grade 3 to 4 hematologic toxicity in 49% to 55% of the bolus arms versus 4% in the PVI arm. No disease-free survival (DFS) or OS difference was detected (3-year DFS, 67% to 69% and 3-year OS, 81% to 83% in all arms). Locoregional failure (LRF) at first relapse was 8% in arm 1, 4.6% in arm 2, and 7% in arm 3. LRF in T1-2, N1-2, and T3, N0-2 primaries who received low anterior resection (those most suitable for primary resection) was 5% in arm 1, 3% in arm 2, and 5% in arm 3. CONCLUSION: All arms provide similar relapse-free survival and OS, with different toxicity profiles and central catheter requirements. LRF with postoperative therapy is low, justifying initial resection for T1-2, N0-2 and T3, and N0-2 anterior resection candidates.

Adult↗
PubMed2006

Phase II trial of R115777 (NSC #70818) in patients with advanced colorectal cancer: a Southwest Oncology Group study.

PURPOSE: The purpose of this Phase II multi-institutional trial was to determine the efficacy and toxicity of R115777 in previously untreated patients with metastatic colorectal carcinoma. PATIENTS AND METHODS: Patients were required to have histologically confirmed colorectal cancer with distant metastatic disease that was not surgically curable. They could not have received prior chemotherapy for metastatic disease. R115777 was given at a dose of 300 mg p.o. twice a day for 21 days every 28 days until tumor progression or toxicity or other reason for discontinuation occurred. The primary endpoint was to determine the confirmed response probability with this treatment. RESULTS: There were 55 eligible patients accrued to the study. There were no complete responses, but one confirmed partial response for a confirmed response probability of 2% (95%CI 0-10%). Three additional patients had an unconfirmed partial response for an overall response probability of 7%. The time to treatment failure was 1.7 months and the estimated median survival was 8.1 months. One patient died of treatment related infection and there were 7 other patients with grade 4 toxicities consisting of neutropenia, leukopenia, febrile neutropenia and thrombocytopenia, depression, increased bilirubin, anemia, and pneumonitis/infiltrates. CONCLUSION: R115777 given as a single agent by this dose and schedule is ineffective in patients with metastatic colorectal cancer.

Adult↗
PubMed2006

Phase II trial of PN401, 5-FU, and leucovorin in unresectable or metastatic adenocarcinoma of the stomach: a Southwest Oncology Group study.

From February, 2001 to September, 2002, the Southwest Oncology Group (SWOG) accrued 65 patients with advanced gastric adenocarcinoma to a phase II trial of weekly 5-FU, leucovorin, and the orally-administered uridine analog PN401. Of these 65 patients, 57 were assessable for survival and toxicity, which were the endpoints for the study. Treatment consisted of the administration of 1200 mg/m(2) of 5-FU, 500 mg/m(2) of leucovorin, and 6 grams of PN401 every 8 h, beginning 8 h after the completion of the 5-FU infusion, and continuing for a total of 8 doses (48 grams) during each weekly chemotherapy session. Therapy was delivered for six weeks out of every 8-week treatment cycle. The gastrointestinal toxicity of this regimen was mild with 2 patients experiencing grade 3 stomatitis, and 6 patients having grade 3 diarrhea; and the hematologic toxicity was acceptable with 6 of 57 patients found to have had grade 3 or 4 leukopenia, and 14 of 57 patients experiencing grade 3 or 4 neutropenia. There were two deaths judged possibly related to treatment; one in a patient who experienced a variety of Grade 2 gastrointestinal toxicities and died at home with an unknown cause of death; and a second patient who also died at home, and for whom treatment-related sepsis could not be ruled out. The overall median survival was 7.2 months. The ability to safely deliver twice the usual dose of 5-FU with leucovorin on a weekly schedule suggests that oral uridine analog supplementation with PN401 may enhance the therapeutic index of the fluoropyrimidines.

Acetates↗
PubMed2005

Impact of the year 2000 Medicare policy change on older patient enrollment to cancer clinical trials.

PURPOSE: A prior analysis by the Southwest Oncology Group (SWOG) showed that women and African American patients were adequately represented on cancer clinical treatment trials but that older patients were substantially underrepresented. Twenty-five percent of patients > or = 65 years old were enrolled onto SWOG trials from 1993 to 1996, whereas 63% of all patients with cancer were > or = 65 years old. Recognition of this under-representation led to a change in Medicare policy in 2000 to include coverage of routine patient care costs of clinical trials. We conducted an updated analysis of accrual trends. METHODS: The proportions of enrollment onto SWOG treatment trials by sex, race/ethnicity, and age (> or = 65 years) were computed for the years 1997 to 2000; corresponding rates in the United States were derived from US Census and National Cancer Institute Surveillance, Epidemiology, and End results data. Additionally, method of payment data were analyzed over time (1993 to 2003) to assess whether patterns in method of payment changed with the new Year 2000 Medicare policy on clinical trials coverage. RESULTS: The results showed continued adequate representation by sex and race/ethnicity. Older patient accrual on SWOG trials increased significantly since 2000, with 31% of patients > or = 65 years old enrolled from 1997 to 2000 and 38% enrolled from 2001 to 2003 (v 25% from 1993 to 1996). The percentage of patients using Medicare plus supplemental insurance also increased beginning in 2000, whereas the percentage of patients using Medicare alone remained the same. CONCLUSION: Method of payment analyses provided evidence that the Year 2000 Medicare policy change had a positive impact, but only for those patients with supplemental private coverage of coinsurance costs. Improvements in the Medicare payment structure could further increase older patient participation in clinical trials.

Aged↗
PubMed2005

Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089.

PURPOSE: In 1990, fluorouracil (FU) plus levamisole for 1 year became standard adjuvant treatment for patients with high-risk stages II and III colon cancer. Intergroup (INT) 0089 assessed the relative contributions of leucovorin and levamisole in such patients. PATIENTS AND METHODS: From 1988 to 1992, 3,794 patients were randomly assigned. Experimental treatment consisted of one of three chemotherapy regimens: the low-dose leucovorin plus FU (Mayo Clinic; LDLV) regimen, the high-dose leucovorin plus FU (Roswell Park; HDLV) regimen, and the low-dose leucovorin plus levamisole plus FU (LDLV plus LEV) regimen, each administered for 30 to 32 weeks. The control arm was levamisole plus FU (LEV) for 1 year. RESULTS: After a median follow-up of 10 years, of 3,561 eligible patients, 1,691 (47%) have died and 1,330 (37%) have experienced disease recurrence; 137 (10%) of those experiencing recurrence are still alive. A total of 481 patients (13%) died without evidence of recurrence, and 1,723 (48%) are alive and disease free. Although there were toxicity differences among the four arms, none was statistically superior in disease-free or overall survival. CONCLUSION: The 6- to 8-month regimens of LDLV and HDLV without levamisole used in this trial, rather than the previous standard regimen of 12 months of LEV, have become widely used. INT-0089 has long-term follow-up of the largest clinical trial of patients with high-risk colon cancer, documenting not only the durability of the treatment effects, but also the natural history of patients with high-risk colon cancer, and analyses of treatment based on age, race, and comorbid conditions such as obesity, diabetes, and second primary cancers.

Adenocarcinoma↗
PubMed2005

Colon cancer survival is associated with decreasing ratio of metastatic to examined lymph nodes.

PURPOSE: Colorectal cancer is the second leading cause of cancer deaths in the United States, with poor survival predicted by regional lymph node (LN) metastasis. The impact of LN ratio (LNR) on survival is unknown in this disease. PATIENTS AND METHODS: We analyzed data from Intergroup trial 0089 of adjuvant chemotherapy for stage II and III patients with colon cancer, in which all patients received fluorouracil-based therapy. Survival was similar for all arms of the study, allowing us to evaluate all patients together. End points included overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS). Multivariate analyses were performed on all patients and on groups according to LNR quartiles (LNR: < 0.05, 0.05 to 0.19, 0.2 to 0.39, and 0.4 to 1.0). Covariates included in the models were age, sex, tumor stage, grade, histology, number of positive LNs, number of LNs removed, and LNR. RESULTS: The median age was 63.7 years, and the median number of LNs removed was 11. In the multivariate analysis, LNR was a significant factor for OS, DFS, and CSS in patients with 10 to 15 LN and more than 15 LN removed but not for patients with less than 10 LN removed. Using quartiles, LNR maintained its significance for all three end points when patients were grouped by node status. CONCLUSION: After curative resection for colorectal cancer, the LNR is an important prognostic factor and should be used in stratification schemes for future clinical trials investigating adjuvant treatments.

Adenocarcinoma↗
PubMed2005

A randomized phase III trial of post-operative adjuvant oral fluoropyrimidine versus sequential paclitaxel/oral fluoropyrimidine; and UFT versus S1 for T3/T4 gastric carcinoma: the Stomach Cancer Adjuvant Multi-institutional Trial Group (Samit) Trial.

Paclitaxel, S1 and their combined sequential administration is proposed to be examined installing UFT as an active control of adjuvant chemotherapy for curatively resected T3-4 gastric cancer in a multicenter Phase III trial. The primary endpoint is disease-free survival and the secondary endpoints are incidence of adverse events, overall survival and compliance. The sample size is 370 per treatment arm (1480 in total) for two hypotheses of the superiority of sequential use of paclitaxel followed by oral fluoropyrimidines to fluoropyrimidines (UFT/S1) alone and the non-inferiority of S1 to UFT to be tested by two-by-two factorial design. Abdominal CT or US is performed every 3 months in the first 2 years and every 6 months thereafter for 3 years in total to ensure recurrence data collection. This trial could appraise sequential combination therapy and efficacy of new drugs as adjuvant for gastric cancer treatment.

Administration, Oral↗
PubMed2005

Role of post-operative chemoradiation in resected gastric cancer.

The curative management of gastric adenocarcinoma depends upon complete resection of the primary tumor. In patients with lymph node metastases in the resected specimen, the relapse and death rates from recurrent cancer are at least 70%-80%. There is continued debate over whether more extensive lymph node dissection (D2) improves survival when compared to less extensive operations. Until recently, attempts at preventing recurrence have employed adjuvant chemotherapy and have been ineffective. A large U.S. Intergroup study (INT-0116) demonstrated that combined chemoradiation following complete gastric resection improves median time to relapse (30 vs. 19 months, P < 0.0001) and overall survival (35 vs. 28 months, P = 0.01). The improvements in disease-free and overall survival resulting from post-operative chemoradiation have defined a new standard of care. An update of the results of INT-0116 analysis performed in 2004 with 7 years median follow-up, not only confirms the benefits from post-operative chemoradiation but also shows that chemoradiation does not produce significant long-term toxicity. The recent publication of the first large adequately powered III neoadjuvant chemotherapy trial suggested this technique might down-stage tumors and increase resectability. Future advances in the therapy of resectable gastric cancer may come from studies of pre-operative neoadjuvant chemoradiation and the application of targeted therapies such as growth receptor antagonists and anti-angiogenesis agents.

Adenocarcinoma↗
PubMed2005

Phase III Southwest Oncology Group 9415/Intergroup 0153 randomized trial of fluorouracil, leucovorin, and levamisole versus fluorouracil continuous infusion and levamisole for adjuvant treatment of stage III and high-risk stage II colon cancer.

PURPOSE: Modest toxicity and possibly enhanced activity makes continuous-infusion fluorouracil (FU) an attractive alternative to FU plus leucovorin (FU/LV) for the adjuvant treatment of colorectal cancer. Intergroup trial 0153 (Southwest Oncology Group trial 9415) was developed to compare the efficacy of continuous-infusion FU (CIFU) plus levamisole to FU/LV plus levamisole in the adjuvant treatment of high-risk Dukes' B2 and C1 or C2 colon cancer. PATIENTS AND METHODS: After surgery, patients were randomly assigned to CIFU 250 mg/m(2)/d for 56 days every 9 weeks for three cycles or FU 425 mg/m(2) and LV 20 mg/m(2) daily for 5 days every 28 to 35 days for six cycles. All patients received levamisole 50 mg tid for 3 days every other week. The primary end point was overall survival (OS). RESULTS: The study closed in December 1999 after an interim analysis demonstrated little likelihood of CIFU showing superiority to FU/LV within the stipulated hazard ratio. A total of 1,135 patients were registered. At least one grade 4 toxicity occurred in 39% of patients receiving FU/LV and 5% of patients receiving CIFU. However, almost twice as many patients receiving CIFU discontinued therapy early compared with those receiving FU/LV. The 5-year OS is 70% (95% CI, 66% to 74%) for FU/LV and 69% (95% CI, 64% to 73%) for CIFU. The corresponding 5-year disease-free survival (DFS) is 61% (95% CI, 56% to 65%) and 63% (95% CI, 59% to 68%), respectively. For all patients, 5-year OS is 83%, 74%, and 55%; 5-year DFS is 78%, 67%, and 47% for N0, N1, and N2-3, respectively. CONCLUSION: CIFU had less severe toxicity but did not improve DFS or OS in comparison with bolus FU/LV.

Adult↗
PubMed2005

Differences in toxicity between men and women treated with 5-fluorouracil therapy for colorectal carcinoma.

BACKGROUND: Recent explorations suggest that women may experience more severe 5-fluorouracil (5-FU)-related toxicity than men. The patient populations from 4 Southwest Oncology Group colorectal carcinoma trials with 5-FU-containing regimens were examined for toxicity differences between the genders. METHODS: The current study included 1074 patients from 4 trials. Hypotheses regarding differences in specific toxicities were generated via exploratory analyses on the data from the 2 earlier trials (n = 505 patients), using basic univariate techniques and classification tree methods. Validation of these hypotheses was performed on data from the 2 later trials (n = 569 patients) using logistic regression models for dichotomous toxicity outcomes and rank-sum tests for comparisons of overall toxicity grade. RESULTS: 5-FU toxicity was more extensive in women than in men in terms of average maximum toxicity grade (P = 0.005), number of different types of toxicity experienced (P = 0.009), and incidence of severe toxicities (P = 0.02). The incidence of > or = Grade 2 hematologic toxicity in the 2 later trials was higher in women than in men and women experienced more frequent moderate to severe mucositis compared with men. CONCLUSIONS: Differences in 5-FU toxicity profiles between men and women were hypothesized after an exploratory analysis, and then verified by an independent confirmatory analysis using data from the 2 later trials. This process provided substantial evidence for gender differences in specific aspects of 5-FU toxicity that persist across a range of treatment regimens, patient characteristics, and cancer trial settings.

Adenocarcinoma↗
PubMed2005

A phase II study of farnesyl transferase inhibitor R115777 in pancreatic cancer: a Southwest oncology group (SWOG 9924) study.

Ninety per cent of pancreatic adenocarcinomas (PC) contain mutations of the K-Ras proto-oncogene resulting in constitutively activated Ras protein. A critical step in Ras activation is farnesylation of Ras protein. Farnesyl transferase inhibitors are compounds that inhibit farnesylation. We report the results of a phase II trial of R115777, an oral farnesyl transferase inhibitor, in patients with surgically incurable locally advanced or metastatic PC. Between 6/1/2000 and 11/20/2001, 58 cases were accrued, 53 of whom were eligible and analyzable. Patients were required to have a performance status (PS) 0 to 1, be able to take oral medications, and to have adequate renal, hepatic, and hematologic functions. Fifty-five percent were male. Median age was 64.7 years (38.9 to 80.6), and patients had no previous systemic therapy for advanced PC. Treatment consisted of R115777 300 mg po bid given for 3 out of every 4 weeks. Toxicities were as follows: Grade 3 in 19/53 (36%), grade 4 in 53 (173%), and grade 5 in 53 (8%). Most frequent toxicities were: anemia 35/53 (66%), fatigue and malaise 33/53 (62%), nausea 31/53 (58%). Grade 5 toxicities included: thromboembolism 1, infection 2, other 1. Median survival was 2.6 months (mo) (95% CI 2.1-3.6), 6-mo survival is 19% (95% CI, 8-29%), median time to treatment failure was 1.4 mo (95% GI 1.1-1.6). R115777 is ineffective as monotherapy in advanced pancreatic cancer.

Adenocarcinoma↗
PubMed2005

Assessment of infusional 5-fluorouracil schedule and dose intensity: a Southwest Oncology Group and Eastern Cooperative Oncology Group study.

BACKGROUND: Building on results from Southwest Oncology Group trial 8905, this trial was designed to compare low-dose continuous infusion (LDCI) of 5-fluorouracil (5-FU) versus intermittent high-dose infusion (HDI) of 5-FU in disseminated colorectal cancer (CRC) for evidence of survival advantage based on dose intensity. A companion trial was funded to assess molecular parameters associated with fluoropyrimidine response or resistance and toxicity from these treatments. PATIENTS AND METHODS: Eligibility included histologic diagnosis of disseminated CRC, measurable or evaluable disease, no previous therapy for metastatic disease, performance status of 0-2, and adequate renal, hepatic, cardiac, and hematologic function. Stratification factors were measurable versus evaluable disease, performance status of 0/1 versus 2, presence versus absence of adjuvant therapy, and presence versus absence of previous surgery and enrollment on the companion trial. Patients were randomized to receive (1) LDCI 5-FU 300 mg/m(2) per day for 28 days every 5 weeks or (2) HDI 5-FU 2,600 mg/m(2) for 24 hours each week. RESULTS: Between April 1995 and May 1999, 730 patients were accrued (LDCI arm, n = 360; HDI arm, n = 370). Of these, 708 eligible patients were assessable for survival and 690 for toxicity. Median survival for both groups was 13 months. Toxicity was mild; < 10% of patients in both arms had grade > 4 events. There were 8 study-related deaths (1%). Less than 10% of patients were enrolled in the companion trial. CONCLUSIONS: Increasing 5-FU dose intensity yields no survival advantage beyond that achieved with LDCI 5-FU. This study confirms the favorable toxicity profile of infusional 5-FU. Because no preferential benefit was observed for either infusion schedule, the more convenient weekly schedule should be considered for 5-FU-based combination regimens for disseminated CRC.

Adolescent↗
PubMed2004

Impact of body mass index on outcomes and treatment-related toxicity in patients with stage II and III rectal cancer: findings from Intergroup Trial 0114.

PURPOSE: To study the relationship between body mass index (BMI) and rates of sphincter-preserving operations, overall survival, cancer recurrence, and treatment-related toxicities in patients with rectal cancer. PATIENTS AND METHODS: We evaluated a nested cohort of 1,688 patients with stage II and III rectal cancer participating in a randomized trial of postoperative fluorouracil-based chemotherapy and radiation therapy. RESULTS: Obese patients were more likely to undergo an abdominoperineal resection (APR) than normal-weight patients (odds ratio, 1.77; 95% CI, 1.27 to 2.46). When analyzed by sex, increasing adiposity in men was a strong predictor of having an APR (P <.0001). Obese men with rectal cancer were also more likely than normal-weight men to have a local recurrence (hazard ratio [HR], 1.61; 95% CI, 1.00 to 2.59). In contrast, obesity was not predictive of cancer recurrence in women, nor was BMI predictive of overall mortality in either men or women. Underweight patients had an increased risk of death (HR, 1.43; 95% CI, 1.08 to 1.89) compared with normal-weight patients but no increase in cancer recurrences. Among all study participants, obese patients had a significantly lower rate of grade 3 to 4 leukopenia, neutropenia, and stomatitis and a lower rate of any grade 3 or worse toxicity when compared with normal-weight individuals. CONCLUSION: Increasing BMI in male patients with rectal cancer is associated with a decreased likelihood of sphincter preservation and a higher chance of local recurrence. For both men and women, overweight and obese patients experience less toxicity associated with adjuvant chemoradiotherapy, suggesting that actual body weight dosing of fluorouracil for obese patients is justified.

Antineoplastic Agents↗
PubMed2004

Clinical overview: adjuvant therapy of gastrointestinal cancer.

Adjuvant therapy has been tested widely in the treatment of cancers of the stomach, pancreas, and large bowel. In the USA, the use of postoperative chemoradiation in stomach cancer is considered a standard of care after the publication of the Intergroup Study 0116 in September 2001. This study demonstrated significant benefit in overall and disease-free survival for patients receiving postoperative treatment with fluorouracil (5-FU)/leucovorin chemotherapy and radiation after gastric resection. Adjuvant chemotherapy is not considered to be of significant benefit, and such therapy for patients with resected gastric cancer is investigational. There is interest in the use of neoadjuvant chemotherapy strategies as preoperative treatment followed by surgical resection. This approach has been tested in a randomized study of over 500 patients carried out by the Medical Research Council in the UK. This study demonstrated that patients receiving preoperative and postoperative epirubicin, cisplatin, 5-FU (ECF) chemotherapy, had a downstaging of tumor size, an increase in rates of curative resection, and an increase in disease-free but not overall survival. With pancreatic cancer, there is a controversy over postoperative chemoradiation after pancreatic resection. A recently completed Intergroup Study compared gemcitabine to 5-FU chemotherapy given before and after radiation in resected pancreatic cancer. Over 500 patients have been accrued to this study, which recently closed. In Western Europe, the results of a large clinical trial (ESPAC) have suggested that chemoradiation is not beneficial in patients with resected pancreatic cancer. In large bowel cancer, 5-FU-based adjuvant chemotherapy regimens are superior to surgery alone, particularly in node-positive patients. The use of newer combinations including 5-FU/leucovorin plus irinotecan and 5-FU/ leucovorin plus oxaliplatin are also of interest as chemotherapy in resected colon cancer patients. The recent publication of the MOSAIC trial demonstrated that 5-FU/leucovorin/oxaliplatin (FOLFOX 4) improves progression-free survival in node-positive patients over 5-FU/leucovorin alone. The results of studies of 5-FU/ leucovorin and irinotecan both in Europe (PETACC) and the USA (IFL vs 5-FU/leucovorin) are awaited with interest. Another area of interest in resected colon cancer is the use of molecular genetic monitoring to assess the likelihood of patient relapse. The data over the past several years have demonstrated that patients whose tumors do not have deletion of the deleted in colon cancer (DCC) gene on chromosome 18 have an improved outcome. Recent data are available with tumors that demonstrate microsatellite instability (MSI). Such tumors represent about 15% of all colon cancers and have an improved outcome when compared to those not expressing MSI, and may not benefit from adjuvant chemotherapy.

Chemotherapy, Adjuvant↗
PubMed2004

Gemcitabine and cisplatin for patients with metastatic or recurrent esophageal carcinoma: a Southwest Oncology Group Study.

PURPOSE: Experimental data, both in vivo and in vitro, suggest that the combination of gemcitabine and cisplatin acts synergistically. Within the Southwest Oncology Group, we designed a Phase II trial to test this chemotherapy combination for patients with esophageal cancer. EXPERIMENTAL DESIGN: Patients with metastatic or recurrent esophageal cancer were treated with gemcitabine 1000 mg/m(2) on days 1, 8, and 15, and cisplatin 100 mg/m(2) on day 15. Cycles were repeated every 28 days. The statistical endpoint was overall survival. RESULTS: Sixty-four eligible patients were accrued from 37 institutions. Twenty-six percent of patients had prior chemotherapy. The treatment was generally well-tolerated, with the most common toxicity being neutropenia in 31% of patients. All 64 patients have died. Survival at 3 months was 81%, and at 1 year was 20%. Median survival was 7.3 months. CONCLUSIONS: This regimen is tolerable palliative option for patients with metastatic esophageal cancer.

Adenocarcinoma↗
PubMed2004

A phase II study of high-dose 24 hour continuous infusion 5-FU and leucovorin and low-dose PALA for patients with advanced pancreatic adenocarcinoma: a Southwest Oncology Group Study.

PURPOSE: The purpose of this phase II multi-institutional study was to define the efficacy and toxicity of infusional 5-FU in combination with PALA and leucovorin in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Patients were required to have histologically confirmed pancreatic cancer that was locally advanced, unresectable or disseminated. The treatment regimen consisted of weekly 5-FU 2600 mg/m(2) given concurrently with leucovorin at 500 mg/m(2). Both drugs were administered by 24-hour continuous infusion. PALA was administered 24 hours prior to the administration of 5-FU/LV at a dose of 250 mg/m(2) IV over 15 minutes weekly. Patients were continued on the assigned treatment regimen until progression of disease, unacceptable toxicity, or the patient declined further therapy. RESULTS: This study accrued 30 patients. Four of these patients were ineligible. All 26 eligible patients were evaluated for toxicity. One patient had inadequate assessment of response and was considered a non-responder. Three of the twenty-six eligible patients had partial responses, for a response rate of 12% (95% confidence interval 2% to 30%). All 26 eligible patients have died and the median overall survival was 7 months (95% confidence interval: 5.2 to 9 months). Four patients experienced grade 4 toxicities, including bilirubin increase (2 patients), vomiting (1 patient) and non-local skin ulceration (1). Two patients discontinued therapy due to toxicity. CONCLUSION: The dual modulation of 5-FU with PALA and leucovorin in the dose and schedule used here, has a response rate similar to other single agents in pancreatic cancer and can result in some long term survival while having relatively mild toxicity.

Adenocarcinoma↗