Cyclophosphamide-cisplatin versus cyclophosphamide-carboplatin in stage III-IV ovarian carcinoma: a comparison of equally myelosuppressive regimens.

Between March 1985 and January 1987, 103 women with histologically proven stage III-IV ovarian carcinoma were randomly allocated to groups receiving monthly intravenous regimens of 1 g of cyclophosphamide/m2 plus either 60 mg of cisplatin (CDDP)/m2 or 150 mg of carboplatin (CBDCA)/m2 for 1 year unless disease progressed earlier. The groups were well balanced according to the stratification factors (age, histologic differentiation, extent of residual disease, and performance score), and both treatments were well tolerated and produced similar median first-course leukopenia (2,200 and 2,000 cells/microL) and thrombocytopenia (220,000 and 202,500 cells/microL). The CBDCA regimen was less emetogenic. After an interim analysis in January 1987 revealed superior progression-free survival for the group of 53 patients receiving CDDP (P = .005), the study was closed to further accrual. Those 24 patients still receiving CBDCA were encouraged to cross over to the CDDP-based regimen and 21 of them did. Following treatment crossover, the relative risk of death associated with original allocation to CBDCA receded from 1.79 to 0.97, indicating success of the salvage treatment using the CDDP-based regimen. This aborted study demonstrated the superiority of CDDP over CBDCA when the two platinum compounds were compared at equally myelosuppressive low doses in combination with 1 g of cyclophosphamide/m2. If CDDP is to be supplanted by CBDCA, larger, more myelosuppressive doses of CBDCA will be required. The platinum drug antitumor effect is a critically important therapeutic feature of this combination.

Hepatic toxicity associated with fluorouracil plus levamisole adjuvant therapy.

PURPOSE: To determine the frequency and nature of hepatic toxicity associated with fluorouracil (5-FU) plus levamisole adjuvant therapy. PATIENTS AND METHODS: All patients had resection of stage II or stage III colon cancer and were randomized to receive observation only, levamisole alone, or 5-FU plus levamisole. Serial liver function studies were documented in 1,025 patients who did not develop recurrence during the year of therapy. RESULTS: One hundred forty-nine (39.6%) of 376 patients treated with 5-FU plus levamisole showed laboratory abnormalities consistent with hepatic toxicity, compared with 16.3% of 251 patients treated with levamisole alone and 16.1% of 398 untreated controls. Most common was elevation of alkaline phosphatase, frequently accompanied by elevations of transaminase or serum bilirubin. Characteristically, these changes were mild, not associated with symptoms, and resolved when therapy was stopped. In some instances, they were associated with elevated carcinoembryonic antigen (CEA) tests or with fatty liver seen on computed tomographic (CT) scan or liver biopsy. CONCLUSION: Mild and reversible hepatotoxicity is a common consequence of 5-FU plus levamisole adjuvant therapy, but this is only rarely symptomatic. However, the oncologist should be alert to this phenomenon, since the associated laboratory and imaging findings may simulate those associated with hepatic metastasis.

Prospective evaluation of prognostic variables from patient-completed questionnaires. North Central Cancer Treatment Group.

PURPOSE: This study was developed to determine whether descriptive information from a patient-completed questionnaire could provide prognostic information that was independent from that already obtained by the patient's physician. PATIENTS AND METHODS: An initial detailed questionnaire was administered to approximately 150 patients with advanced cancer. This questionnaire was subsequently revised and given to a total of 1,115 patients with advanced colorectal or lung cancer. Univariate and multivariate analyses were performed to evaluate the data from these questionnaires. RESULTS: A total of 36 variables showed statistically significant prognostic information for survival in univariate analyses, even though many of these variables were associated with only a minimal increase in risk. A multivariate analysis demonstrated that there was a high correlation between many variables. Three major groups of variables became apparent as providing strong prognostic information. These included the following: (1) a physician's assessment of performance status (PS); (2) a patient's assessment of their own PS; and (3) a nutritional factor such as appetite, caloric intake, or overall food intake. CONCLUSION: Data generated by a patient-completed questionnaire can provide important prognostic information independent from that obtained by other physician-determined prognostic factors.

A controlled evaluation of combined 5-fluorouracil, doxorubicin, and mitomycin C (FAM) for the treatment of advanced non-small-cell lung cancer.

One hundred eighty-six patients with advanced non-small-cell lung cancer were randomly assigned to treatment with combined 5-fluorouracil, doxorubicin, and mitomycin C (FAM) or combined methotrexate, doxorubicin, cyclophosphamide, and lomustine (MACC). Respective objective regression rates were comparable at 20% and 16%. Distribution of intervals to progression (overall median, 2.8 months) and survival times (overall median, 5.0 months) were essentially identical between the two regimens. The comparability of therapeutic effect was also evident within the subset of 81 patients who had adenocarcinoma cell type, although MACC showed a small advantage in survival after covariate analysis. In large-cell carcinoma, MACC showed a higher regression rate than that of FAM as well as a small advantage in survival. In squamous-cell carcinoma, however, FAM was superior to MACC in regression rates (32% v 4%) and also provided somewhat longer survival. With regard to toxicity, MACC produced a higher incidence of nausea and vomiting, whereas FAM produced more frequent and severe thrombocytopenia. From an overall standpoint, the therapeutic accomplishments of both regimens were disappointing. Our study does, however, provide additional evidence that mitomycin C-containing regimens may be selectively effective for squamous-cell carcinoma of the lung.

A controlled evaluation of recent approaches to biochemical modulation or enhancement of 5-fluorouracil therapy in colorectal carcinoma.

Three hundred thirty-five previously untreated patients with advanced colorectal carcinoma were randomly assigned to treatment with 5-fluorouracil (5-FU) alone, 5-FU plus N-(phosphonacetyl)-L-aspartic acid (PALA), 5-FU plus high-dose thymidine, 5-FU plus levamisole, or 5-FU plus methyl CCNU, vincristine, and streptozotocin (MOF-Strept). Dosages were designed to produce definite toxicity in the majority of patients, although the nature of dose-limiting reactions varied considerably among regimens. 5-FU alone and 5-FU plus levamisole produced mucocutaneous reactions, diarrhea, and leukopenia; 5-FU plus PALA produced primarily mucocutaneous reactions and diarrhea; 5-FU plus thymidine produced leukopenia with occasional neurotoxicity and hypotension; and MOF-Strept produced substantial nausea and vomiting with both thrombocytopenia and leukopenia. Objective response rates among patients with measurable disease varied from 12% (5-FU plus PALA) to 34% (MOF-Strept), but none of the regimens were significantly superior to 5-FU alone. Both interval to progression and survival were comparable among the five regimens with no reasonable chance that any combination regimen could produce as much as a 50% improvement when compared with 5-FU alone. Whereas we observed definite modulation of 5-FU dose--toxicity relationships, particularly with the thymidine and PALA combinations, this did not result in a detectable improvement in therapeutic effect. None of the combination regimens, administered in the dosages and schedules we used, can be recommended as standard therapy of advanced colorectal carcinoma.

Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer.

PURPOSE: To determine the effectiveness of fluorouracil plus levamisole administered postoperatively to patients with resected stage II (Dukes' B2) colon cancer. PATIENTS AND METHODS: This randomized controlled clinical trial (INT-0035) was performed by National Cancer Institute-sponsored cancer clinical trials cooperative groups. Patients were assigned to observation only or to fluorouracil (450 mg/m2 intravenously [IV] daily for 5 days and, beginning at 28 days, weekly for 48 weeks) plus levamisole (50 mg orally three times daily for 3 days repeated every 2 weeks for 1 year). Cancer recurrence, survival, and treatment side effects were assessed. RESULTS: Three hundred eighteen eligible patients were analyzed with a median follow-up time of 7 years. Fluorouracil plus levamisole reduced the recurrence rate by 31%, although this trend was not statistically significant (P = .10). A total of 87 patients died: 43 on observation and 44 on fluorouracil plus levamisole. Disparity between effects on recurrence rate and overall survival is partially explained by a higher rate of non-colon cancer-related deaths on fluorouracil plus levamisole (15 v seven) and by the effects of salvage surgery with curative intent. Of seven patients with recurrence who were rendered disease-free by salvage surgery, six were on the observation arm. As was observed in patients treated with fluorouracil plus levamisole for stage III disease, toxicity was acceptable and compliance was excellent. CONCLUSION: Fluorouracil plus levamisole is tolerable and accepted as standard surgical adjuvant therapy for patients with stage III colon cancer, but the data from this study in stage II patients suggest a decreased relapse rate without a significant improvement in survival.

Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. The North Central Cancer Treatment Group and the Mayo Clinic.

A total of 401 eligible patients with resected stages B and C colorectal carcinoma were randomly assigned to no-further therapy or to adjuvant treatment with either levamisole alone, 150 mg/d for 3 days every 2 weeks for 1 year, or levamisole plus fluorouracil (5-FU), 450 mg/m2/d intravenously (IV) for 5 days and beginning at 28 days, 450 mg/m2 weekly for 1 year. Levamisole plus 5-FU, and to a lesser extent levamisole alone, reduced cancer recurrence in comparison with no adjuvant therapy. These differences, after correction for imbalances in prognostic variables, were only suggestive for levamisole alone (P = .05) but quite significant for levamisole plus 5-FU (P = .003). Whereas both treatment regimens were associated with overall improvements in survival, these improvements reached borderline significance only for stage C patients treated with levamisole plus 5-FU (P = .03). Therapy was clinically tolerable with either regimen and severe toxicity was uncommon. These promising results have led to a large national intergroup confirmatory trial currently in progress.

Biochemical modulation of fluorouracil: evidence of significant improvement of survival and quality of life in patients with advanced colorectal carcinoma.

The purpose of this study was to evaluate the effectiveness of several new approaches designed to enhance the activity of fluorouracil (5-FU) in the management of advanced colorectal cancer. A total of 429 patients were randomized to one of the following regimens: single-agent 5-FU, given by standard 5-day, intensive-course intravenous bolus technique; 5-FU plus high-dose folinic acid (leucovorin) or 5-FU plus low-dose leucovorin; 5-FU plus high-dose methotrexate (MTX) with oral leucovorin rescue; 5-FU plus low-dose MTX; and 5-FU plus cisplatin (CDDP). The median survival for patients receiving 5-FU alone was 7.7 months. The high- and low-dose leucovorin plus 5-FU regimens had median survivals of 12.2 and 12.0 months, respectively, and offered a significant survival advantage over 5-FU alone with one-sided P values of .037 and .050, respectively (P = .051 for each treatment after correction for prognostic variables). The only other regimen possibly associated with improved survival was high-dose MTX plus 5-FU, with a median survival of 10.5 months (P = .21, P = .076 corrected). In addition, both high- and low-dose leucovorin plus 5-FU regimens were associated with significantly improved tumor response rates (P = .04 and .001) and significantly improved interval-to-tumor-progression rates (P = .015 and .007) when compared with 5-FU alone. Only the low-dose leucovorin plus 5-FU regimen was associated with significant (P less than .05) superiority in each of the following parameters of quality of life: performance status, weight gain, and symptomatic relief. The overall most therapeutically favorable regimen in this trial was 5-FU given with low-dose leucovorin; fortuitously, this regimen is associated with very low drug cost. Whereas this is the first study to demonstrate both improved palliation and survival for any regimen compared with 5-FU given by rapid intravenous (IV) injection for 5 consecutive days at a dose of 500 mg/m2/d in patients with advanced colorectal cancer, the magnitude of the gain is still relatively small. Our low-dose leucovorin plus 5-FU regimen is currently being studied in a national trial with the hope that this increased advanced disease activity may produce more substantive gains in the surgical adjuvant setting.

Prospectively randomized trial of postoperative adjuvant chemotherapy in patients with high-risk colon cancer.

PURPOSE: This study had two major goals: (1) to assess the effectiveness of a regimen of fluorouracil (5-FU) plus levamisole plus leucovorin as postoperative surgical adjuvant therapy for patients with high-risk colon cancer, and (2) to evaluate 6 months versus 12 months of chemotherapy. PATIENTS AND METHODS: Patients with poor-prognosis stage II or III colon cancer were randomly assigned to receive adjuvant chemotherapy with either intensive-course 5-FU and leucovorin combined with levamisole, or a standard regimen of 5-FU plus levamisole. Patients were also randomly assigned to receive either 12 months or 6 months of chemotherapy, which resulted in four treatment groups. RESULTS: Eight hundred ninety-one of 915 patients entered (97.4%) were eligible. The median follow-up duration is 5.1 years for patients still alive. There was a difference among the four treatment groups with respect to patient survival, and a significant duration-by-regimen interaction was observed. Specifically, standard 5-FU plus levamisole was inferior to 5-FU plus leucovorin plus levamisole when treatment was given for 6 months (5-year survival rate, 60% v 70%; P < .01). CONCLUSION: There was no significant improvement in patient survival when chemotherapy was given for 12 months compared with 6 months. When chemotherapy was given for 6 months, standard 5-FU plus levamisole was associated with inferior patient survival compared with intensive-course 5-FU plus leucovorin plus levamisole. These data suggest that 5-FU plus levamisole for 6 months should not be used in clinical practice, whereas 6 months of treatment with 5-FU plus leucovorin plus levamisole is effective.

Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity.

PURPOSE: Considerable pilot data and clinical experience suggested that an aloe vera gel might help to prevent radiation therapy-induced dermatitis. METHODS AND MATERIALS: Two Phase III randomized trials were conducted. The first one was double blinded, utilized a placebo gel, and involved 194 women receiving breast or chest wall irradiation. The second trial randomized 108 such patients to aloe vera gel vs. no treatment. Skin dermatitis was scored weekly during both trials both by patients and by health care providers. RESULTS: Skin dermatitis scores were virtually identical on both treatment arms during both of the trials. The only toxicity from the gel was rare contact dermatitis. CONCLUSIONS: This dose and schedule of an aloe vera gel does not protect against radiation therapy-induced dermatitis.

Randomized clinical trial of doxorubicin alone or combined with mitolactol in women with advanced breast cancer and prior chemotherapy exposure.

One hundred fifty-one women with advanced breast cancer who had failed prior chemotherapy were randomized to monthly courses of doxorubicin (60 mg/m2 I.V. day 1, observation after 500 mg/m2) or doxorubicin (40 mg/m2 I.V. day 1; maximum 500 mg/m2) and mitolactol (135 mg/m2 orally, days 1-10; 180 mg/m2 after maximum doxorubicin). Median survival times were 232 days for doxorubicin and 225 days for doxorubicin + mitolactol, and median times to progression were 112 days and 97 days, respectively. Results are inconsistent with a 25% improvement in survival or time to progression for doxorubicin + mitolactol (p = 0.04 and 0.02, respectively, adjusted for stratification factors but not multiple testing). Regression rates for all patients, both measurable and evaluable, were 30% for doxorubicin alone and 26% for doxorubicin + mitolactol. Regression rates were significantly higher in patients with measurable indicator lesions. Cardiac toxicity was seen in four patients, all of whom were receiving doxorubicin alone. It appears that the combination of doxorubicin + mitolactol is not substantially more effective than doxorubicin alone in women with advanced breast cancer and prior chemotherapy exposure.

An evaluation of the carcinoembryonic antigen (CEA) test for monitoring patients with resected colon cancer.

OBJECTIVE: To determine the effectiveness of carcinoembryonic antigen (CEA) monitoring in detecting surgically curable recurrence of colon cancer. DESIGN: Clinical data were collected from a national surgical adjuvant trial in which CEA monitoring was elective. SETTING: Cancer centers, universities, and community clinics. PATIENTS: A total of 1216 patients with resected colon cancer, 1017 (84%) of whom had CEA monitoring. MAIN OUTCOME MEASURES: Sensitivity and specificity of CEA testing for cancer recurrence and CEA-motivated diagnostic and surgical interventions and their end results. RESULTS: Among 417 monitored patients with recurrence, 59% had a preceding elevation of CEA concentration. Sixteen percent of 600 patients without recurrence showed a false-positive test result. Carcinoembryonic antigen testing was most sensitive for hepatic or retroperitoneal metastasis and relatively insensitive for local, pulmonary, or peritoneal involvement. Surgical explorations were performed in 115 patients with CEA elevations, and 47 recurrences, usually hepatic, were resected with curative intent. On the other hand, 38 patients with normal CEA concentrations and 23 patients not monitored also underwent such resections--usually for pulmonary or local recurrence. Of all CEA-monitored patients, 2.3% are alive and disease free more than 1 year after salvage surgery (2.9% of those with CEA elevations and 1.9% of those with no elevations). Of patients with no CEA monitoring, 2.0% are also alive and disease free more than 1 year after salvage surgery. CONCLUSIONS: Cancer cures attributable to CEA monitoring are, at best, infrequent. It is questionable whether this small gain justifies the substantial cost in dollars and physical and emotional stress that this intervention may cause for patients.

Phase II study of bisantrene administered by continuous 72-hour infusion for advanced pancreatic adenocarcinoma.

Eighteen ambulatory patients who had proven metastatic adenocarcinoma of the pancreas and measurable disease but no previous chemotherapy were treated with bisantrene given by constant central intravenous infusion over 72 hours at a total dose of 300 mg/m2 repeated every 3 to 4 weeks. No objective regression was seen. The median interval to progression was 6 weeks; the median survival was 14 weeks. Primary toxic reactions were nausea, vomiting, and leukopenia. In no instance were these life-threatening. When administered by the method we used, bisantrene cannot be recommended for treatment of advanced pancreatic adenocarcinoma.

A phase II evaluation of menogaril in cisplatin-refractory advanced ovarian carcinoma. A collaborative trial of the North Central Cancer Treatment Group and the Mayo Clinic.

Forty-one women with advanced, recurrent epithelial ovarian carcinoma (in whom prior chemotherapy with a platinum-based regimen failed) were treated with menogaril 200 mg/m2 intravenously every 4 weeks in a Phase II trial. Partial responses were seen in two of 19 (10.5%) measurable disease patients and three of 12 (25%) nonmeasurable but evaluable patients, an overall objective response rate of 16.1% (95% confidence interval, 5% to 34%). Median time to progression for all patients was 2 months and median survival, 5 months. Toxicities were acceptable and consisted primarily of leukopenia and gastrointestinal toxicity. Twenty-nine percent of the patients had venous irritation or painful phlebitis at the intravenous injection site. Menogaril, as administered in this protocol, had modest antineoplastic activity in previously treated ovarian carcinoma patients. The responses were of short duration, and there appeared to be no survival advantage with menogaril treatment.

An evaluation of postoperative follow-up tests in colon cancer patients treated for cure.

BACKGROUND: Currently patients with colon cancer who are potentially cured by surgery are followed periodically with physical examinations, blood tests and imaging studies to detect tumor recurrence early, on the presumption that intervention can effect outcome. There is little information to indicate whether frequent visits to the doctor's office or frequent testing improves survival or quality of life. METHODS: Ninety-eight patients with resected stage B2, B3 or C (modified Astler-Coller) colon cancer who developed recurrent disease while enrolled in prospective adjuvant trials at Mayo Clinic sponsored by the North Central Cancer Treatment Group were studied to evaluate the utility of follow-up tests to detect the first recurrence of colon cancer and the outcome following various interventions for these recurrences. These patients had a history, physical examination, complete blood count, chemistry panel and chest x-ray approximately every 3-4 months in the 1st year and then every 6-12 months thereafter for a total of 5 years. Bowel evaluation was done at 6 months, 12 months and annually thereafter. In addition, a minority of patients had carcinoembryonic antigen (CEA) testing, and radioisotope liver scans at various intervals. RESULTS: Symptoms signaled the diagnosis of recurrent disease in 55 patients, physical examination in 4 patients, and abnormalities in chest x-ray in 18 patients. An elevated CEA was the initial abnormal test in 5 patients, abnormal liver scans in 5 patients, elevated liver function tests in 6 patients and laparotomy for other reasons in 2 patients. Hemoglobin, barium enema, and fecal blood testing were useful in 1 patient each. Thirty-one percent of recurrences were diagnosed between scheduled visits. In our series, histories, physical examinations, and chest x-rays led to the detection of 79% of the recurrences while liver function tests, liver scans and CEAs led to the detection of 16% of recurrences. Sixteen patients underwent resection for cure for their first recurrence; the diagnosis of recurrence was signaled by symptoms in 6 patients, chest x-ray in 6 patients and abnormal liver function tests, CEA, hemoglobin, and laparotomy for colostomy closure in 1 patient each. CONCLUSIONS: The majority of tumor recurrences were detected by symptoms, physical examinations and chest x-rays. Testing for asymptomatic tumor recurrences during the 1st follow-up year is likely to be much less fruitful for detecting resectable recurrences than testing patients in the 2nd through 4th follow-up years. Patients who had a disease recurrence in the 1st postoperative year were less likely to be candidates for curative intent surgery. Lower tumor grade at initial diagnosis correlated both with likelihood of undergoing secondary surgical resection and the chance of doing well following this. These data may be helpful for defining more appropriate follow-up test for detection of tumor recurrence in patients with resected colon cancer.

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.

Randomized clinical trial of cyclophosphamide, 5-FU, and prednisone with or without tamoxifen in postmenopausal women with advanced breast cancer.

The purpose of this study was to determine if tamoxifen added to the efficacy of a CFP (cyclophosphamide, 5-FU, and prednisone) regimen. One hundred thirty-one postmenopausal women with advanced breast cancer without prior chemotherapy exposure were randomized to receive CFP alone or combined with tamoxifen; six were disqualified because of ineligibility. Objective responses were seen in 68% of the eligible patients receiving CFP and in 61% of those receiving CFP plus tamoxifen. Median times to progression were 287 days for CFP and 158 days for CFP plus tamoxifen (two-sided log-rank test of equality of progression distributions, P = 0.07). Median survival times were 544 days for CFP and 394 days for CFP plus tamoxifen (two-sided log-rank test of equality of survival distributions, P = 0.14). The addition of tamoxifen to CFP was not associated with longer time to progression or survival in any Cox covariate model. On the basis of our data, it can be concluded that the addition of tamoxifen to CFP does not substantially improve either the time to disease progression or survival in women with metastatic breast cancer.

Phase II evaluation of menogaril in patients with advanced cervical carcinoma. A collaborative trial of the North Central Cancer Treatment Group and Mayo Clinic.

Fourteen patients with advanced/recurrent squamous cell carcinoma of the uterine cervix received menogaril, 200 mg/m2 by one hour intravenous infusion at four-week intervals. No objective regressions were observed. Median time to progression was less than two months and median survival was seven months. All patients experienced neutropenia. Platelet toxicity was negligible. Venous irritation and phlebitis occurred at the infusion site in 43% of patients. Menogaril as administered in this protocol is ineffective in treating previously irradiated advanced/recurrent squamous cell carcinoma of the uterine cervix and warrants no further investigation in this disease at the dosage and administration schedule used in this protocol.

Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report.

OBJECTIVE: To determine the effectiveness of two adjuvant therapy regimens in improving surgical cure rates in stage III (Dukes stage C) colon cancer. DESIGN: Randomized, concurrently controlled clinical trial. SETTING: Major cancer centers, universities, and community clinics affiliated with the North Cancer Treatment Group, the Southwest Oncology Group, and the Eastern Cooperative Oncology Group. PATIENTS: Those who had had curative-intent resections of stage III colon cancer in the previous 1 to 5 weeks. INTERVENTION: Patients were assigned to observation only, to levamisole alone (50 mg orally three times/d for 3 days, repeated every 2 weeks for 1 year), or to this regimen of levamisole plus fluorouracil (450 mg/m2 body surface area intravenously daily for 5 days and then, beginning at 28 days, weekly for 48 weeks). MEASUREMENTS: Rates of cancer recurrence and death. Early- and late-treatment side effects. RESULTS: With all 929 eligible patients able to be followed for 5 years or more (median follow-up, 6.5 years), fluorouracil plus levamisole reduced the recurrence rate by 40% (P < 0.0001) and the death rate by 33% (P = 0.0007). Levamisole reduced the recurrence rate by only 2% and the death rate by only 6%. With few exceptions, toxicity was mild and patient compliance was excellent. No evidence of late side effects was seen. CONCLUSION: Fluorouracil plus levamisole is tolerable adjuvant therapy to surgery; it has been confirmed to substantially increase cure rates for patients with high-risk (stage III) colon cancer. It should be considered standard treatment for all such patients not entered into clinical trials.

Pilot study of accelerated hyperfractionated thoracic radiation therapy in patients with unresectable stage III non-small cell lung carcinoma.

BACKGROUND: The primary goal of this study was to determine the incidence of severe or greater acute radiation toxicity, and secondarily, response, survival, and local control in patients with unresectable Stage IIIA or B non-small cell lung cancer treated with accelerated hyperfractionated thoracic radiation therapy (AHTRT). METHODS: From September, 1989 through March, 1990, 21 evaluable patients with unresectable Stage IIIA or B non-small cell lung cancer were treated with AHTRT, using 6000 cGy in 40 fractions of 150 cGy twice daily, 6 hours between fractions, with a 2-week break midway through treatment. RESULTS: Two patients (9.5%) had acute Grade 3 radiation esophagitis requiring intravenous hydration, and two patients (9.5%) had acute Grade 3 radiation pneumonitis requiring oxygen and steroids. Only one patient had chronic toxicity, a Grade 3 radiation pneumonitis. Five patients (24%) achieved a complete response, whereas eight (38%) had a partial response or regression. With minimum follow-up of nearly 3 years, 3 patients are alive and 18 are dead. The median survival time and 1-, 2-, and 3-year survival rates were 10.8 months, 48%, 29%, and 14%, respectively. Local control was achieved in 11 of 21 (52%) patients. CONCLUSIONS: This AHTRT regimen can be given with an acceptable incidence of acute radiation toxicity. Response, survival, and local control rates in this unfavorable group of patients are encouraging. A North Central Cancer Treatment Group Phase III study of standard thoracic radiation therapy (6000 cGy in 30 fractions of 200 cGy daily) versus AHTRT (+/- chemotherapy) is now open.