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D C Tormey

Publications and source records attributed to D C Tormey.

At least 19 recordsLinked to original sources
PubMed1992

Continuous-infusion 5-fluorouracil combined with doxorubicin and cyclophosphamide: feasibility study.

Previous studies have demonstrated continuous-infusion 5-fluorouracil (CI 5-FU) to be an active single-agent treatment for breast cancer without significant myelotoxicity. These qualities made CI 5-FU an attractive agent for combination with other effective but myelosuppressive agents. In this study we attempted to determine the maximal doses of CI 5-FU that could be added to a combination of agents known to be dose limited by myelotoxicity, doxorubicin 50 mg/m2 day 2 and cyclophosphamide 150 mg/m2 days 3-12 of a 28-day cycle. Patients who received doxorubicin and cyclophosphamide alone developed significant myelotoxicity but did not develop stomatitis. The addition of 5-7 days of CI 5-FU at 200-300 mg/m2 was associated more closely with increased stomatitis (P = .11) than with increased granulocytopenia (P = .57). The stomatitis observed for low doses of CI 5-FU given with doxorubicin and cyclophosphamide would not have been expected for these low doses of CI 5-FU given as a single agent. We conclude that the addition of CI 5-FU to myelotoxic doses of doxorubicin and cyclophosphamide is not a promising therapeutic strategy for significantly increasing the effectiveness of this combination of agents.

Adenocarcinoma↗
PubMed1992

Overexpression of HER-2/neu and its relationship with other prognostic factors change during the progression of in situ to invasive breast cancer.

Using permanent-section immunohistochemistry, we investigated the role of HER-2/neu in the development and progression of human breast cancer by measuring its overexpression in a series of hyperplastic (n = 30), dysplastic (n = 15), and malignant neoplastic (n = 708) lesions of ductal epithelium and by evaluating the relationships between overexpression and clinicopathologic features known to have prognostic significance in these lesions. The neoplasms included pure ductal carcinoma in situ (DCIS; n = 59) and infiltrating ductal carcinoma (IDC; n = 649). The latter were all node negative and stratified into IDC combined (n = 237) or not combined (n = 412) with a "significant amount" of DCIS (defined as DCIS greater than or equal to 10% of total tumor cellularity). Overexpression of HER-2/neu was not observed in any of the hyperplastic or dysplastic lesions. In contrast, it was present in 56% of pure DCIS and in 77% of the comedo subtype of this group. Only 15% of IDC overexpressed HER-2/neu. However, the rate of overexpression was significantly higher in the subset of IDC combined with DCIS compared with the subset of IDC not combined with DCIS (22% v 11%, respectively; P less than .0001). These results are consistent with the hypothesis that HER-2/neu plays a more important role in initiation than in progression of ductal carcinomas. They also suggest that overexpression decreases within individual tumors as they evolve from in situ to increasingly invasive lesions or, alternatively, that many invasive carcinomas arise de novo (ie, without progressing through a significant in situ stage) by mechanisms not involving HER-2/neu. In addition, overexpression of HER-2/neu was associated with several poor prognostic features (younger patient age, premenopause, negative estrogen receptor status, negative progesterone receptor status, and high nuclear grade) in the subset of IDC combined with DCIS. With one exception (negative estrogen receptor status) these associations were lost in IDC not combined with DCIS, also suggesting that the role of HER-2/neu changes during the progression of human breast cancer.

Biomarkers, Tumor↗
PubMed1992

Phase II trials of interferons-alpha and -beta in advanced sarcomas.

Interferons (IFNs)-alpha and -beta were administered to patients with metastatic sarcomas in two different Eastern Cooperative Oncology Group studies. In one study, patients received IFN-alpha 2b, 20 million units/m2 i.v. 5 days/week x 4, then 10 million units s.c.t.i.w. In the second study, patients received IFN-beta ser 180 million units t.i.w. Of 87 patients evaluable for response, there were three responses in 64 patients (5%) treated with IFN-alpha-2b and no responses in 23 patients treated with IFN-beta ser. Severe or life-threatening fatigue with decline in performance status complicated treatment of 37% of patients receiving IFN-alpha 2b and 17% of patients receiving IFN-beta ser. Further investigation of IFNs in sarcomas should depend on evidence from preclinical studies demonstrating synergistic effects of IFNs combined with a cytoreductive modality which has proven activity in these malignancies.

Adult↗
PubMed1992

Influence of estradiol and tamoxifen on susceptibility of human breast cancer cell lines to lysis by lymphokine-activated killer cells.

The design of combination hormonal and immunotherapeutic protocols for breast cancer patients may be facilitated by analysis of preclinical in vitro model systems. Estrogen receptor positive (ER+: MCF-7) and negative (ER-: MDA-MB-231) human breast cancer cell lines were utilized to evaluate the effects of tamoxifen (TAM) and estradiol (E2) on modulation of breast cancer target susceptibility to lysis by lymphokine-activated killer (LAK) cells. E2-stimulated ER+ cells were more susceptible to lysis by LAK cells than corresponding TAM-treated or control cells, while treatment of ER- cells with either E2 or TAM alone did not alter from control their susceptibility to this immune-mediated lysis. All ER+ and ER- cells tested remained sensitive after treatment with TAM to lysis by LAK cells. In addition, an adenocarcinoma reactive human-mouse chimeric monoclonal antibody (ING-1) was able to significantly boost in vivo generated LAK cell-mediated lysis of control, E2-treated, and TAM-treated ER+ and ER- cells. These in vitro results provide a preclinical rationale for in vivo testing of TAM, interleukin-2 (IL-2), and breast cancer reactive antibody-dependent cellular cytotoxicity facilitating antibody in patients with refractory or high risk breast cancer.

Antibodies, Monoclonal↗
PubMed1992

Adjuvant therapy with a doxorubicin regimen and long-term tamoxifen in premenopausal breast cancer patients: an Eastern Cooperative Oncology Group trial.

PURPOSE: A randomized trial was performed in premenopausal postoperative women with ipsilateral axillary node-positive (N+) breast carcinoma and known estrogen receptor (ER) status to assess the efficacy of an Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH)-based induction regimen and 5 or more years of tamoxifen (Tam). PATIENTS AND METHODS: Patients received 12 28-day cycles of cyclophosphamide 100 mg/m2 orally days 1 to 14, methotrexate 40 mg/m2 intravenously (IV) days 1 and 8, fluorouracil 600 mg/m2 IV days 1 and 8, prednisone 40 mg/m2 orally days 1 to 14, and Tam 10 mg orally twice daily (CMFPT), or the same regimen plus halotestin 10 mg orally twice daily (CMFPTH) alternating monthly with 22-day cycles of vinblastine 4.5 mg/m2 IV day 1, Adriamycin 45 mg/m2 IV day 1, thiotepa 12 mg/m2 IV day 1, halotestin, and Tam (ALTER). Prednisone in the ALTER regimen was stopped after the second CMFPTH cycle. After 12 cycles, patients were again randomized to stop or continue Tam. After 5 years, patients on Tam were again randomized to continue or stop Tam; the results from this randomization are still coded. Among 533 analyzed induction cases, 263 received CMFPT and 270 ALTER. Among 396 analyzed maintenance cases, 201 continued Tam and 195 were observed. Pretreatment characteristics were balanced among treatments. The median follow-up times are 5.1 years for induction and 4.1 years for maintenance. RESULTS: The time to relapse (TTR) was superior for the ALTER regimen (P = .04) and for the maintenance Tam (P = .05). Overall survival comparisons between the regimens are not statistically different. A longer TTR was associated with decreasing nodal involvement, ER+ status, and increasing age. The favorable effects of decreasing nodal involvement and ER+ status carried over to survival; a progesterone receptor-positive (PgR+) status and decreasing tumor size were also associated with longer survival. Development of amenorrhea was associated with improved TTR and survival. Toxicity was similar for the two induction regimens and for the two maintenance regimens. Overall relapse patterns were similar among the induction regimens, but continuing Tam led to fewer locoregional relapses. CONCLUSION: The results suggest significant overall TTR therapeutic benefits of an Adriamycin-containing alternating induction regimen and of continuing maintenance Tam therapy for at least 5 years.

Adult↗
PubMed1992

Prognostic significance of S-phase fraction in good-risk, node-negative breast cancer patients.

PURPOSE: Formalin-fixed, paraffin-embedded tissues from axillary node-negative breast cancer patients were analyzed by flow cytometry to determine the prognostic significance of DNA ploidy and S-phase fraction (SPF). PATIENTS AND METHODS: All patients were registered on a good-risk control arm of an intergroup clinical trial. They had small- to intermediate-sized (less than 3 cm), estrogen receptor (ER)-positive tumors and received no adjuvant therapy after modified radical mastectomy or total mastectomy with low axillary-node sampling. The median follow-up was 4.8 years. RESULTS: Assessable ploidy results were obtained from 92% of the 298 specimens studied (51% diploid, 49% aneuploid), and SPFs were assessable for 83% of the tumors. SPFs for diploid tumors ranged from 0.7% to 11.9% (median, 3.6%), compared with a range of 1.2% to 26.7% (median, 7.6%) for aneuploid tumors (P less than .0001). No significant differences in disease-free or overall survival were observed between patients with diploid and aneuploid tumors. Using different SPF cutoffs by ploidy status (4.4% for diploid, 7.0% for aneuploid), patients with low SPFs had significantly longer disease-free survival rates than patients with high SPFs (P = .0008). The actuarial 5-year relapse rates were 15% and 32% for patients with low (n = 142) and high SPFs (n = 105), respectively. Similar relationships between SPF and clinical outcome were observed for patients with diploid tumors (P = .053) and for patients with aneuploid tumors (P = .0012). CONCLUSION: S-phase fraction provides additional prognostic information for predicting disease-free survival for axillary node-negative breast cancer patients with small, ER-positive tumors.

Actuarial Analysis↗
PubMed1992

HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma.

PURPOSE: Amplification and/or overexpression of the HER-2/neu oncogene have been shown to correlate with poor clinical outcome in patients with axillary node-positive breast cancer. In contrast, the prognostic significance of HER-2/neu in node-negative disease is controversial. This study was undertaken to evaluate further the relationship between HER-2/neu and clinical outcome in node-negative disease. PATIENTS AND METHODS: Overexpression of HER-2/neu was evaluated by permanent-section immunohistochemistry in tumors from 613 patients with long-term clinical follow-up enrolled in the Intergroup Study 0011. Patients were stratified into low-risk (n = 307) and high-risk (n = 306) groups on the basis of tumor size and estrogen-receptor (ER) status. Low-risk patients were defined as having small (less than 3 cm), ER-positive tumors and were observed without additional treatment after initial surgery. High-risk patients had either ER-negative or large (greater than or equal to 3 cm), ER-positive tumors and were randomized to be observed (n = 146) or to receive adjuvant chemotherapy (n = 160) after surgery. RESULTS: The rate of HER-2/neu overexpression was 14.3% in all tumors combined and was higher in invasive carcinomas with (21.5%) than without (11.2%) a significant noninvasive or in situ histologic component (P less than .0001). There was no relationship between overexpression and clinical outcome in the natural history setting of combined low-risk and high-risk patients not receiving adjuvant therapy (n = 453). Based on the reasoning that the influence of HER-2/neu may have been obscured by high-risk features and/or the presence of noninvasive carcinoma, we also analyzed the subset of patients with low-risk lesions not containing a significant in situ component (n = 179). Patients of this group with HER-2/neu-positive tumors showed only 40% disease-free survival (DFS) at 5 years, compared with over 80% in patients with HER-2/neu-negative tumors (P less than .0001). A similar inverse correlation was observed between overexpression and overall survival in the same group of patients (P = .0001). In a separate analysis involving patients receiving adjuvant chemotherapy, those with HER-2/neu-negative tumors showed significantly improved DFS in response to therapy compared with patients with HER-2/neu-positive tumors. CONCLUSION: Overexpression of HER-2/neu is associated with poor clinical outcome in a subset of node-negative patients with small, ER-positive, predominantly invasive tumors and may play a role in resistance to adjuvant chemotherapy.

Breast Neoplasms↗
PubMed1992

Prognostic potential of DNA flow cytometry measurements in node-negative breast cancer patients: preliminary analysis of an intergroup study (INT 0076).

An ancillary study (INT 0076) to the Intergroup clinical trial of node-negative breast cancer patients (INT 0011) was performed to retrospectively evaluate DNA flow cytometry measurements of ploidy (DNA content) and proliferative capacity (S-phase fraction) for their ability to predict time to recurrence. Of the 915 patients eligible for the clinical trial, 788 were registered for the ancillary flow cytometry study (INT 0076). Four hundred and three of these patients [estrogen receptor (ER)-positive, tumor size less than 3 cm] had been registered to the observation arm of the clinical trial and 385 (ER-negative and/or tumor size greater than or equal to 3 cm) had been randomly assigned to adjuvant chemotherapy (cyclophosphamide, methotrexate, fluorouracil, and prednisone for six cycles) or to observation. Paraffin blocks from 95% (748 of 788) of these patients were obtained, 712 of which had sufficient cancer tissue to be evaluable for the flow cytometric assay. DNA ploidy status (DNA diploid vs DNA aneuploid) was evaluable for 565 (79%) specimens, 64% of which were aneuploid. Proliferative capacity was estimated by the percentage of cells having an S-phase DNA content, using a trapezoidal modeling algorithm(s) as previously described. The median S-phase value for the entire group (both registered and randomly assigned patients) was 6.97%, which defined the cutoff for interpretation of high or low S-phase values. With a median follow-up time of 4.55 years, S-phase fraction, but not ploidy status, is a significant predictor for time to recurrence in both the randomly assigned and the untreated population (observed registered group and observed randomly assigned group).(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Neoplasms↗
PubMed1992

Chemotherapy versus observation in high-risk node-negative breast cancer patients.

Postoperative women with breast cancer but without histopathological evidence of metastases to the axillary lymph nodes or clinical evidence of metastases were studied. Six hundred fifty-five "good-risk" patients who were estrogen receptor positive (ER+) with primary tumors less than 3 cm were registered for observation. Twenty-four of these patients were treated with chemotherapy. Five hundred thirty-six "poor-risk" patients who were either ER+ with primary tumors greater than or equal to 3 cm or estrogen receptor negative (ER-) with any primary tumor size were randomly assigned between chemotherapy and observation. Randomization was stratified by type of surgical procedure, number of lymph nodes examined, menopausal status, tumor size, and ER status. The chemotherapy (CMFP) consisted of six 4-week cycles of cyclophosphamide, 100 mg/m2 orally days 1-14; methotrexate, 40 mg/m2 intravenously (IV) days 1 and 8; fluorouracil, 600 mg/m2 IV days 1 and 8; and prednisone, 40 mg/m2 orally days 1-14. Treatment arms in the randomly assigned patients were balanced with respect to pretreatment characteristics. This analysis includes 445 eligible patients entered in the registration arm and 425 eligible patients entered into the randomized treatments. The median follow-up is 4.5 years in the randomly assigned cohort and 4.8 years in the registered cohort. The overall 5-year disease-free survival (DFS) among the randomly assigned patients was 83% with CMFP and 61% with observation (P less than .0001). A DFS treatment benefit was observed in premenopausal and postmenopausal patients as well as in patients with ER+ or ER- tumors. There were fewer local-regional and distant relapses among the CMFP-treated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Continuous infusion 5-fluorouracil with escalating doses of intermittent cisplatin and etoposide. A phase I study.

Continuous infusion 5-fluorouracil (CI 5-FU) and the combination of cisplatin (CDDP) plus etoposide (VP-16) have emerged as salvage regimens for metastatic breast carcinoma (MBC). In this study, 18 patients (15 with MBC) were entered into a Phase I study to determine the maximum intermittent doses of CDDP and VP-16 that could be added to 200 mg/m2/d CI 5-FU. The maximum tolerated dose of the combination was 40 mg/m2 of CDDP and 60 mg/m2 of VP-16 weekly for the first 8 weeks and every other week thereafter. The dose-limiting toxicities of the regimen were myelosuppression and thrombocytopenia. Two complete responses (both patients had received no previous chemotherapy) and one partial response were noticed. This regimen at the doses described here is appropriate for Phase II trials as an alternative to doxorubicin-based regimens for MBC.

Adult↗
PubMed1991

Alteration of endocrine parameters in premenopausal women with breast cancer during long-term adjuvant therapy with tamoxifen as the single agent.

Tamoxifen is used to treat selected patients at each stage of breast cancer. Although most clinical experience has been obtained with postmenopausal women, increasing numbers of premenopausal women will be treated with 5 or more years of adjuvant tamoxifen therapy following surgery. Indeed, the proposed use of tamoxifen to prevent breast cancer in high-risk women could result in its extended use during the childbearing years. We have monitored the changes in circulating hormone levels from the ovary and pituitary gland in premenopausal (41-47 years old) women with stage I or II breast cancer during adjuvant therapy with tamoxifen as the single agent for 4-72 months following a mastectomy. Each patient (total eight) continued to menstruate, and ovulation occurred. Circulating levels of luteinizing hormone and follicle-stimulating hormone (except in one woman) remained in the normal range (determined in 12 regularly menstruating women in a control group). The levels of estradiol, estrone, and progesterone were elevated onefold to threefold. Prolactin levels decreased by 30%-40%, but the levels of sex hormone binding-globulin were unaffected. These data demonstrate that premenopausal women taking tamoxifen are potentially at risk for pregnancy and must be counseled about barrier contraception. Furthermore, the impact of many years of ovarian stimulation by tamoxifen must be evaluated, especially in women with node-negative disease or in healthy women in whom tamoxifen is used to prevent breast cancer.

Adult↗
PubMed1991

Organizing multicenter trials: lessons from the cooperative oncology groups.

The execution of cancer clinical therapy trials has evolved over the past 45 years and is centered in the Clinical Oncology Group mechanism. The organization, statistical and administrative support, protocol development, and quality control systems have been worked out well and can be described in detail through the Eastern Cooperative Oncology Group. Prevention trials, on the other hand, are larger and fewer and take longer to complete. They involve people who are healthy or not as motivated to take pills or change lifestyle habits as those who are ill. The problems of compliance, toxicity, and costs become major issues. The practice of medicine is organized to take care of sick people and not healthy volunteers. We describe potential roles for Clinical Oncology Groups. These include preliminary tests of prevention agents for safety and toxicity much like Phase 1 trials with cytotoxic agents. A second important possible involvement would be to provide patients at high risk for developing second cancers, treatment- or non-treatment-induced, for prevention trials. A third set of individuals that can be recruited through current group resources are relatives of cancer patients who themselves might be highly motivated to participate in prevention trials. While the Clinical Oncology Groups may not have primary roles in prevention trials, they do represent a resource that has trial discipline and willingness and could facilitate the research efforts in chemoprevention.

Clinical Protocols↗
PubMed1991

Long-term survival of patients treated with combination chemotherapy for metastatic breast cancer.

Long-term survival of patients with metastatic breast cancer treated on two prospective stratified randomised trials has been analysed. Patients on study B122 received either cyclophosphamide, methotrexate and 5-fluorouracil (CMF) or cyclophosphamide, doxorubicin and 5-fluorouracil (CAF). On study B141 patients received CAF or mitolactol (dibromodulcitol), doxorubicin and vincristine alternating after every three cycles with three cycles of CMF (DAV/CMF). Long-term follow-up of 172 patients showed no significant survival difference (in multivariate regression models) for treatment with either CMF vs. CAF or CAF vs. DAV/CMF. The difference in median survival times between CMF and CAF showed a trend in favour of CAF. Advances in the management of metastatic breast cancer in postmenopausal women obtained by doxorubicin regimens have had a small but measurable impact on survival, but known patient discriminants were not overridden by the treatment regimens investigated in these studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

A pilot study of three sequential chemotherapeutic regimens in metastatic breast cancer.

The aim of this pilot study was to estimate the toxicity and response rate of an alternating chemotherapeutic program in chemotherapy-naive metastatic breast cancer patients. Treatment consisted of regimen A (given days 1-28): cyclophosphamide 100 mg/m2 PO days 1-14, doxorubicin 30 mg/m2 i.v. days 1 and 8, and 5-fluorouracil 500 mg/m2 i.v. days 1 and 8 (CAF regimen); regimen B (given days 29-56): dibromodulcitol 135 mg/m2 p.o. days 30-39, mitoxantrone 9 mg/m2 i.v. day 29, and vincristine 1.2 mg/m2 i.v. (maximum 2.0 mg) day 29 (DMV regimen); and regimen C (given days 57-84): thiotepa 12 mg/m2, doxorubicin 45 mg/m2 and vinblastine 4.5 mg/m2 all i.v. on day 57. There were 27 eligible patients with a median age of 51 years (range 34-78). On 14 episodes the leukocyte count fell to less than 1 X 10(9)/L during the first six cycles of treatment (14% of 99 cycles). There were no treatment-related deaths. Common non-life-threatening toxicities included thrombocytopenia, anemia, vomiting, and alopecia. Despite having no drugs in common, the leukocyte and platelet nadirs after CAF correlated with the nadir counts after DMV (r values of 0.6829 and 0.5892, respectively; p = 0.01). Among the 23 patients with measurable and/or evaluable disease there were five complete responses (22%) and nine partial responses (39%), with a median time to treatment failure of 29 weeks. The overall median survival was 19 months.

Adult↗
PubMed1991

Phase I study of toremifene in patients with advanced cancer.

A phase I multicenter evaluation of a novel antiestrogen, toremifene, was undertaken in postmenopausal women with various advanced difficult-to-treat malignancies. One hundred and seven women were treated at one of six dosage levels (10, 20, 40, 60, 200, or 400 mg/d orally) for at least 8 weeks. Weekly evaluations for toxicity were conducted. The most common side effects were nausea (31%), vomiting (12%), and hot flashes (29%). Five patients were removed from the study for possible adverse reactions: three patients experienced hypercalcemia; one experienced tremulousness, fatigue, and inability to think clearly; and one had vaginal bleeding. Twelve patients died while on study, 11 with disease progression and one with a pulmonary embolus. Sex hormone-binding globulin (SHBG) levels increased and there was a modest decline in serum antithrombin III levels. Four of 48 assessable patients had partial responses: three with breast cancer and one with endometrial cancer. Toremifene was generally well tolerated at the doses tested.

Adult↗
PubMed1991

Venous and arterial thrombosis in patients who received adjuvant therapy for breast cancer.

The records of 2,673 patients randomized according to seven consecutive Eastern Cooperative Oncology Group (ECOG) studies of adjuvant therapy for breast cancer were reviewed for the occurrence of vascular complications. All protocols opened and closed between June 1977 and July 1987. The objectives of the present study were (1) to compare the frequency of vascular complications among patients who received adjuvant therapy for breast cancer with patients on observation, and (2) to estimate the contribution of chemotherapy and hormonal therapy to the occurrence of venous and arterial thrombi. The frequency of thrombosis, both venous and arterial combined, was 5.4% among patients who received adjuvant therapy and was 1.6% among patients on observation (P = .0002). Premenopausal patients who received chemotherapy and tamoxifen had significantly more venous complications than those who received chemotherapy without tamoxifen (2.8% v 0.8%, P = .03). Postmenopausal patients who received tamoxifen and chemotherapy had significantly more venous thrombi than those who received tamoxifen alone (8.0% v 2.3%, P = .03) or those who were observed (8.0% v 0.4%, P less than .0001). Premenopausal patients who received tamoxifen and chemotherapy had a 1.6% frequency of arterial thrombosis, significantly more than patients who received chemotherapy alone (1.6% v 0.0%, P = .004). The frequency of arterial thrombosis among postmenopausal patients was not significantly correlated with adjuvant therapy. In conclusion, patients who received adjuvant therapy for breast cancer had a 5.4% frequency of thromboembolic complications, significantly more than those who were observed. The combination of chemotherapy and tamoxifen was associated with more venous and arterial thromboembolic complications than chemotherapy alone in premenopausal patients and with more venous thrombi than tamoxifen alone among postmenopausal patients.

Aged↗
PubMed1990

Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma.

Twelve hundred ninety-six patients with resected colon cancer that either was locally invasive (Stage B2) or had regional nodal involvement (Stage C) were randomly assigned to observation or to treatment for one year with levamisole combined with fluorouracil. Patients with Stage C disease could also be randomly assigned to treatment with levamisole alone. The median follow-up time at this writing is 3 years (range, 2 to 5 1/2). Among the patients with Stage C disease, therapy with levamisole plus fluorouracil reduced the risk of cancer recurrence by 41 percent (P less than 0.0001). The overall death rate was reduced by 33 percent (P approximately 0.006). Treatment with levamisole alone had no detectable effect. The results in the patients with Stage B2 disease were equivocal and too preliminary to allow firm conclusions. Toxic effects of levamisole alone were infrequent, usually consisting of mild nausea with occasional dermatitis or leukopenia, and those of levamisole plus fluorouracil were essentially the same as those of fluorouracil alone--i.e., nausea, vomiting, stomatitis, diarrhea, dermatitis, and leukopenia. These reactions were usually not severe and did not greatly impede patients' compliance with their regimen. We conclude that adjuvant therapy with levamisole and fluorouracil should be standard treatment for Stage C colon carcinoma. Since most patients in our study were treated by community oncologists, this approach should be readily adaptable to conventional medical practice.

Adolescent↗