Defining the optimal therapy for rectal cancer.
Explore the source record for details and available documents.
Combined Modality Therapy↗
Biomedical subjects
D G Haller
Publications and source records attributed to D G Haller.
A phase II trial of 5-fluorouracil, leucovorin, and interferon alpha 2A (IFN-alpha 2a) in metastatic pancreatic carcinoma: a Penn Cancer Clinical Trials Group (PCCTG) trial.
A phase II study was performed to evaluate the activity and toxicity of 5-fluorouracil (5-FU), leucovorin, and inteferon alpha-2a in metastatic pancreatic carcinoma. Twenty-three patients were entered in this study. Four patients withdrew before receiving treatment and one patient was nonevaluable for response because of treatment-related toxicity. The most common significant toxicity was nausea and vomiting. Treatment-related hospitalization was significant. Of 18 evaluable patients, 4 maintained stable disease and 14 had disease progression. None had an objective clinical response. We conclude that this biochemically modulated 5-FU regimen is ineffective treatment for advanced pancreatic carcinoma, with significant toxicity even in highly selected patients with an ambulatory performance status.
Adult↗
Adjuvant active specific immunotherapy for stage II and III colon cancer with an autologous tumor cell vaccine: Eastern Cooperative Oncology Group Study E5283.
PURPOSE: A randomized phase III clinical trial of adjuvant active specific immunotherapy (ASI) with an autologous tumor cell-bacillus Calmette-Guérin (BCG) vaccine was conducted to determine whether surgical resection plus ASI was more beneficial than resection alone in stage II and III colon cancer patients. PATIENTS AND METHODS: Patients (n = 412) with colon cancer (297 with stage II disease, 115 with stage III disease) were randomly allocated to an observation arm or to a treatment arm in which they received three weekly intradermal vaccine injections of 10(7) irradiated autologous tumor cells beginning approximately 4 weeks after surgery. The first two weekly injections also contained 10(7) BCG organisms. Patients were observed for determination of time to recurrence and disease-free and overall survival. RESULTS: This was a negative study in that after a 7.6-year median follow-up period, there were no statistically significant differences in clinical outcomes between the treatment arms. However, there were disease-free survival (P =.078) and overall survival (P =.12) trends in favor of ASI when treatment compliance was evaluated, ie, patients who received the intended treatment had a delayed cutaneous hypersensitivity (DCH) response to the third vaccination (induration >/=5 mm). Also, the magnitude of the DCH response correlated with improved prognosis. The 5-year survival proportion was 84.6% for those with indurations greater than 10 mm, compared with 45.0% for those with indurations less than 5 mm. CONCLUSIONS: When all randomized patients were evaluated, no significant clinical benefit was seen with ASI in surgically resected colon cancer patients with stage II or III colon cancer. However, there was an indication that treatment compliance with effective immunization results in disease-free and overall survival benefits.
Adjuvants, Immunologic↗
Waiting for the definitive trial of hepatic arterial chemotherapy for colorectal cancer.
Explore the source record for details and available documents.
Antineoplastic Combined Chemotherapy Protocols↗
Postoperative radiation therapy for rectal cancer combined with UFT/leucovorin.
Postoperative combined-modality therapy with fluorouracil (5-FU) and radiation therapy is accepted practice for high-risk rectal cancer. Postoperative pelvic radiotherapy alone may improve pelvic control, but is not associated with an improvement in survival. Protracted infusional 5-FU has been associated with decreased tumor recurrence and improved survival when combined with postoperative adjuvant pelvic radiotherapy. The use of new drugs and alternative ways of administering 5-FU is desirable. UFT plus leucovorin is an oral 5-FU prodrug with efficacy equal to 5-FU plus leucovorin in metastatic colorectal cancer. A combination of postoperative adjuvant UFT plus leucovorin concurrent with radiation therapy should be feasible, and the design of an ongoing phase I trial is presented.
Administration, Oral↗
Safety of oxaliplatin in the treatment of colorectal cancer.
The new platinum compound oxaliplatin (Eloxatin) appears to have activity, either alone or in combination, as both first- and second-line therapy for advanced colorectal cancer. Unlike other platinum derivatives, it is not associated with significant nephrotoxicity or ototoxicity. The addition of oxaliplatin at 85 mg/m2 to a fluorouracil/leucovorin-based regimen administered every 2 weeks is well tolerated. The incidence of diarrhea and stomatitis increases with the addition of oxaliplatin, but can be managed by adjusting the dose. There is also a significantly higher incidence of grade 3 or 4 neutropenia with oxaliplatin. Neutropenic febrile complications are rare. The occurrence of other hematologic, hepatic, or renal toxicities does not increase when oxaliplatin is added to fluorouracil-based regimens. Unlike other agents used for the treatment of colorectal cancer, oxaliplatin causes acute and chronic neurosensory symptoms. These acute symptoms are managed by taking precautions (e.g., avoid cold drinks/food for a few days following treatment). Cumulative neurotoxicity is the dose-limiting toxicity associated with oxaliplatin treatment. This toxicity appears reversible with discontinuation of the drug and typically occurs well after the onset of tumor response.
Antineoplastic Combined Chemotherapy Protocols↗
Phase II trial of trimetrexate for patients with advanced gastric carcinoma: an Eastern Cooperative Oncology Group study (E1287).
BACKGROUND: A Phase II study was conducted to evaluate the response, duration of response, and duration of survival of patients with measurable gastric carcinoma treated with trimetrexate (TMTX) who had not had prior chemotherapy. METHODS: Thirty-three patients with unresectable or metastatic gastric adenocarcinoma who had not received previous chemotherapy were treated with intravenous TMTX 12 mg/m(2) daily for 5 days. The dosage of TMTX was reduced to 8 mg/m(2) daily for 5 days for those who had received prior radiotherapy. The cycle was repeated every 3 weeks until disease progression or unacceptable toxicity occurred. RESULTS: Thirty-three patients could be analyzed with follow-up data. There was one Grade 5 (lethal) toxicity and four Grade 4 toxicities. Hematologic toxicity was the most common. The overall response rate was 21%, the overall median progression free survival was 2.7 months, and the overall median survival was 5.9 months for the entire cohort. No patients were alive at last follow-up. CONCLUSIONS: Though TMTX as a single agent has activity in gastric carcinoma with manageable toxicity, it cannot be recommended for routine use as a single agent due to the brief duration of response and median survival.
Adenocarcinoma↗
The evaluation and treatment of patients receiving radiation therapy for carcinoma of the esophagus: results of the 1992-1994 Patterns of Care Study.
BACKGROUND: For the first time, a Patterns of Care Study (PCS) was conducted in 1992-1994 to determine the national practice standards in evaluating and treating patients with esophageal carcinoma and to determine the degree to which clinical trials have been incorporated into national practice. METHODS: A national survey of 61 institutions using 2-stage cluster sampling was conducted, and specific information was collected on 400 patients with squamous cell carcinoma or adenocarcinoma of the thoracic esophagus who received radiation therapy (RT) as part of definitive or adjuvant management of their disease. Patients were staged according to a modified 1983 American Joint Committee on Cancer staging system. Chi-square tests for significant differences between academic and nonacademic institutions for a particular variable were performed. RESULTS: The median age of patients was 66.7 years (range, 26-89 years); 76.5% were male and 23.5% were female. Karnofsky performance status was > or = 80 for 88.3% of patients. Squamous cell carcinoma was diagnosed in 61.5% and adenocarcinoma in 36.8%. Fifteen percent were Clinical Stage (CS) I, 39.5% CS II, and 29.5% CS III. Evaluative procedures included endoscopy (>93%), computed tomography (CT) of the chest (86%), CT of the abdomen (75%), esophagography (68.5%), and endoscopic ultrasound (3.5%). Endoscopic ultrasound and CT of the chest were performed significantly more frequently at academic than nonacademic facilities (6.1% vs. 1.0% and 91.9% vs. 81.3%, respectively). Three-quarters of all patients received chemotherapy and RT and 62.5% received concurrent chemotherapy and RT as part of their treatment. Treatments included chemotherapy plus RT (54.0%), RT alone (20.3%), preoperative chemotherapy + RT (13.3%), postoperative chemotherapy + RT (7.7%), postoperative RT (3.5%), and preoperative RT (1.2%). The chemotherapeutic agents most frequently used were 5-fluorouracil (84%), cisplatin (64%), and mitomycin (9%); academic instututions used cisplatin significantly more often and mitomycin significantly less often than nonacademic institutions. Brachytherapy was used in 8.5% of cases. The median total dose of external beam radiation was 50.4 gray and the median dose per fraction was 1.8 gray. CONCLUSIONS: This study establishes the national benchmarks for the evaluation and treatment of patients with esophageal carcinoma at radiation facilities in the U.S. It also indicates that the majority of patients given RT as a component of treatment for esophageal carcinoma receive chemoradiation rather than RT alone, as supported by clinical trials. Although some differences in the evaluation of esophageal carcinoma were noted between academic and nonacademic facilities, there was no difference in the frequency of use of chemoradiation versus RT by facility type.
Adenocarcinoma↗
Phase II protocol for the evaluation of new treatments in patients with advanced gastric carcinoma: results of ECOG 5282.
The study was a Phase II randomized study to evaluate the efficacy of new agents for the treatment of advanced gastric carcinoma. Patients were randomized to receive single agent chemotherapy with mitoxantrone, etoposide, aclacinomycin-A or spirogermanium. The patients were stratified by prior use of chemotherapy, prior doxorubicin use and ECOG performance status. Patients with a history of cardiac disease or prior doxorubicin exceeding a dose of 400 mg/m2 were restrictively randomized to sopirogermanium or etoposide only. One hundred and fourteen patients were registered for the study. Among 98 evaluable patients there were only two partial responses (both in the etoposide arm), and one complete response in the mitoxantrone arm. The median survival on the study was 3.3 months. One hundred and six patients were analyzable for toxicity. There were four treatment-related deaths and four life-threatening toxicities. Because of low response rates and relatively high toxicities the studied compounds were not deemed worth further investigation for advanced gastric cancer.
Aclarubicin↗
A phase II trial of homoharringtonine and caracemide in the treatment of patients with advanced large bowel cancer.
Twenty-four previously untreated, ambulatory patients with advanced colorectal carcinoma were treated with either caracemide (11 patients) or homoharringtonine (13 patients). No objective responses were observed in any of the treatment cohorts. Caracemide was well tolerated with the exception of one death due to sepsis. On the homoharringtonine arm one patient died of pulmonary sepsis, one patient experienced grade 4 leukopenia requiring more than 4 weeks of recovery, and an additional patient developed grade 4 renal failure. These severe and unexpected complications caused early termination of accrual to the homoharringtonine arm of the study. These agents have no activity in the treatment of advanced colorectal carcinoma.
Adult↗
Therapy for early-stage colorectal cancer.
Surgery is the only curative option for patients with colorectal cancer. The goal of other modalities, such as chemotherapy, immunotherapy, and radiotherapy, is to prolong survival and reduce the risk of recurrence. Adjuvant treatment is mandatory for patients with stage III colon cancer. At present, 6 months of fluorouracil (5-FU) plus leucovorin (folinic acid) can be considered standard therapy. The data on stage II colon cancer are less convincing, and perhaps only subgroups benefit from adjuvant therapy. Patients with stage II disease should be encouraged to participate in randomized trials. Outside of such trials, one can consider prognostic factors in the decision to offer adjuvant therapy. Patients with T3 or N1-3 M0 rectal cancer should receive combined-modality therapy, i.e., 5-FU-based chemotherapy and irradiation. Until ongoing trials answer the question of whether a patient should be irradiated preoperatively or postoperatively, the type of surgery determines the timing of irradiation. If the tumor is amenable to a sphincter-preserving operation, surgery can be followed by radiation therapy. In patients with fixed tumors and those in whom resectability is an issue, prolonged preoperative radiotherapy is more appropriate. Ongoing trials should optimize existing adjuvant therapy (by achieving an ideal balance between toxicity and effectiveness) and integrate the advantages of recently approved drugs.
Chemotherapy, Adjuvant↗
Adjuvant therapy of colon cancer.
Colon cancer is an important cause of cancer-related mortality. A series of clinical trials of adjuvant systemic therapy have been performed in attempt to establish means to improve outcome in this disease. By the early 1990s, a role for 5-fluorouracil (5-FU)-based chemotherapy in stage III colon cancer had been firmly established. The precise role for chemotherapy in stage II disease remains under investigation. Progress continues toward optimizing the schedule and duration of systemic therapy, allowing for maximal efficacy with a minimum of toxicity. It appears that approximately 6 months of 5-FU and leucovorin are as effective as more prolonged regimens. Levamisole does not appear to add to the benefit of 5-FU and leucovorin. Several newer agents such as the oral fluorinated pyrimidines, irinotecan (CPT-11) and oxaliplatin have demonstrated activity in metastatic colon cancer and hold promise as potentially effective drugs to be tested in the adjuvant setting.
Antineoplastic Agents↗
Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer.
BACKGROUND: We performed a multi-institutional randomized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer. METHODS: Preoperative chemotherapy for patients randomly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil. Surgery was performed two to four weeks after the completion of the third cycle; patients also received two additional cycles of chemotherapy after the operation. Patients randomly assigned to the immediate-surgery group underwent the same surgical procedure. The main end point was overall survival. RESULTS: Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery. After a median possible study time of 55.4 months, there were no significant differences between the two groups in median survival: 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery (P=0.53). At one year, the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone; at two years, survival was 35 percent and 37 percent, respectively. The toxic effects of chemotherapy were tolerable, and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery. There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma. Weight loss was a significant predictor of poor outcome (P=0.03). With the addition of chemotherapy, there was no change in the rate of recurrence at locoregional or distant sites. CONCLUSIONS: Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus.
Adenocarcinoma↗
Combined chemoradiotherapy vs. radiotherapy alone for early stage squamous cell carcinoma of the esophagus: a study of the Eastern Cooperative Oncology Group.
Squamous carcinoma of the thoracic esophagus has an extremely poor prognosis. This study, EST-1282, was undertaken by the Eastern Cooperative Oncology Group (ECOG) to determine whether the combined use of 5-fluorouracil (5-FU), mitomycin C, and radiation therapy improved the disease-free survival and overall survival of patients with carcinoma of the esophagus, compared to those who received radiation therapy alone. Two- and 5-year survivals were 12% and 7% in the radiation alone arm and 27% and 9% in the chemoradiation arm. Patients treated with chemoradiation had a longer median survival (14.8 months), compared to patients receiving radiation therapy alone (9.2 months). This difference was statistically significant. The same pattern of survival was noted in almost all subgroups independent of whether surgical resection was performed.
Analysis of Variance↗
Surgery for recurrent colon cancer: strategies for identifying resectable recurrence and success rates after resection. Eastern Cooperative Oncology Group, the North Central Cancer Treatment Group, and the Southwest Oncology Group.
BACKGROUND: Follow-up testing after surgery for colon cancer is recommended principally to identify resectable recurrences, but data on the efficacy of, outcomes of, and optimal strategies for this testing are limited. OBJECTIVES: To determine the relation between follow-up tests and salvage surgery, assess outcomes, and document surgical mortality. DESIGN: Retrospective cohort study. SETTING: A North American multi-institutional trial comparing postoperative chemotherapy plus follow-up with follow-up alone. PATIENTS: 1247 patients with resected stage II and stage III colon cancer. INTERVENTION: The protocol mandated follow-up testing that could be supplemented at the discretion of treating physicians. Indications of recurrent disease were documented. MEASUREMENTS: Recurrence, resectable recurrence, surgical mortality, and survival were studied. RESULTS: 548 patients had recurrence of colon cancer. Salvage surgery was attempted in 222 patients (41%). In 109 patients (20%), curative-intent surgery was done for hepatic recurrence (28 patients), pulmonary metastasis (20 patients), local recurrence (24 patients), or recurrence at other sites (37 patients). Most curative-intent surgical procedures were motivated by follow-up testing (36 patients), elevated carcinoembryonic antigen level (41 patients), or symptoms (27 patients). The median follow-up time after curative-intent surgery exceeded 5 years; the estimated 5-year disease-free survival rate was 23%. A solitary lesion was a favorable prognostic factor. The surgical mortality rate was 2%. Curative-intent resections were done in 15 patients with second primary colorectal cancer; 12 of these patients have survived disease-free. CONCLUSIONS: Second operations for colon cancer that are triggered by follow-up testing or symptoms are common and can result in long-term disease-free survival.
Colonic Neoplasms↗
Epirubicin has modest single-agent activity in head and neck cancer but limited activity in metastatic melanoma and colorectal cancer: phase II studies by the Eastern Cooperative Oncology Group.
Epirubicin (4'-epidoxorubicin), a diastereoisomer of doxorubicin, has established activity in the treatment of many cancer types sensitive to doxorubicin. Its activity in other tumor targets such as melanoma, head and neck cancer, and recurrent colorectal cancer has been less well defined. Three concurrent phase II studies examined the efficacy and toxicity of epirubicin (90 mg/m2 given intravenously at 3-week intervals) in the treatment of 71 patients with the aforementioned cancers. Of 66 eligible patients who were assessable for response, one patient (with colorectal cancer) achieved a complete response and three patients (with head and neck cancer) achieved partial responses. The response rate in patients with head and neck cancer was 18% (95% confidence interval, 4-43%). Myelosuppression, alopecia, and nausea were the most frequent toxicities. Two patients died of neutropenic sepsis and grade IV leukopenia occurred in six patients (8%). Grade III toxicities were as follows: leukopenia (17%), anemia (10%), alopecia (8%), fever (1%), thrombocytopenia (1%). Grade I or II cardiac toxicity was noted in four patients at cumulative doses ranging between 375 mg/m2 to 1,283 mg/m2. Epirubicin is ineffective as a single agent at this dose and schedule in the treatment of patients with melanoma and colorectal cancer. In head and neck cancer, a modest response rate encourages further exploration of epirubicin and related anthracyclines in combination regimens.
Adult↗
A phase II trial and pharmacokinetic analysis of 96-hour infusional paclitaxel in patients with metastatic colorectal cancer.
A phase II study was conducted to evaluate the activity and toxicity of 96-hour infusional paclitaxel in patients with previously untreated metastatic colorectal cancer. Twelve patients were enrolled in this study. The first patient received a total dose of 140 mg/m2 over 96 hours resulting in grade 4 neutropenia, neutropenic fever, and grade 3 stomatitis. Subsequent patients received a total dose of 120 mg/m2 over 96 hours. Grade 3 to 4 neutropenia occurred in four of these patients. No significant thrombocytopenia was observed. Grade 3 to 4 nonhematologic toxicities in the group treated at 120 mg/m2 over 96 hours included nausea/vomiting in one patient, stomatitis in one patient, and diarrhea in two patients. One patient experienced a possible pulmonary hypersensitivity reaction. None of the 12 patients achieved an objective response. Two patients had stable disease and ten had progressive disease. Pharmacokinetic parameters including maximum plasma concentration and area under the concentration time curve were significantly higher in patients with grade 3 to 4 neutropenia than patients who experienced less toxicity. The authors conclude that further study of 96-hour infusional paclitaxel in patients with metastatic colorectal carcinoma is not warranted.
Aged↗
Postsurgical surveillance of colon cancer: preliminary cost analysis of physician examination, carcinoembryonic antigen testing, chest x-ray, and colonoscopy.
OBJECTIVE: This study is the first to examine the relative and absolute costs of physician examination, carcinoembryonic antigen (CEA) assessment, chest x-ray, and colonoscopy in detecting recurrent disease in patients who have undergone surgical resection for primary colon carcinoma. METHODS: Of the 1356 Eastern Cooperative Oncology Group patients in Intergroup Protocol 0089 who underwent surgical resection for Dukes' B2 and C colon carcinoma, 421 patients who developed recurrent disease were reviewed. Follow-up testing was performed according to protocol guidelines, with the cost of each test equal to 1995 Medicare reimbursement. Follow-up was defined as the time to recurrence for the 421 patients in whom disease recurred (mean 18.6 months) or up to 5 years for the additional 930 patients in whom disease did not recur (mean 38.6 months). Patients were divided into three categories: nonrecurrent, recurrent but not resectable, and recurrent but resectable with curative intent. The estimated mean cost of each test in detecting group 3 (recurrent but resectable) patients was calculated. RESULTS: Of the 421 patients who developed recurrent disease, 96 underwent surgical resection of their disease with curative intent (group 3). For group 3 patients, the first indication of recurrent disease was CEA testing (30), chest x-ray (12), colonoscopy (14), and other (40). Of the 40 "other" patients, 24 presented with symptoms. Routine physician examination, however, failed to identify a single resectable recurrence, and the total cost for physician examination was $418,615. The detection rate for CEA testing was 2.2%, the total cost was $170,880, and the cost per recurrence was $5,696. The detection rate for chest x-ray was 0.9%, the total cost was $120,934, and the cost per recurrence was $10,078. The detection rate of colonoscopy was 1%, the total cost was $641,344, and the cost per recurrence was $45,810. CONCLUSIONS: CEA measurement was the most cost-effective test in detecting potentially curable recurrent disease. Physician visits were useful only in the evaluation of symptoms; a routine physician examination had no added benefit.
Antineoplastic Agents↗