Clinical Trial to Assess the Relative Efficacy of Fluorouracil and Leucovorin, Fluorouracil and Levamisole, and Fluorouracil, Leucovorin, and Levamisole in Patients With Dukes' B and C Carcinoma of the Colon: Results From National Surgical Adjuvant Breast and Bowel Project C-04

1999 ◽  
Vol 17 (11) ◽  
pp. 3553-3559 ◽  
Author(s):  
Norman Wolmark ◽  
Howard Rockette ◽  
Eleftherios Mamounas ◽  
Judy Jones ◽  
Sam Wieand ◽  
...  
Keyword(s):  
Overall Survival ◽  
Disease Free Survival ◽  
Pairwise Comparison ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Carcinoma Of The Colon ◽  
Bowel Project ◽  
Effect Of Treatment ◽  
To Receive ◽  
Dukes C

PURPOSE: To compare the efficacy of leucovorin-modulated fluorouracil (FU+LV) with that of fluorouracil and levamisole (FU+LEV) or with the combination of FU+LV and levamisole (FU+LV+LEV). PATIENTS AND METHODS: Between July 1989 and December 1990, 2,151 patients with Dukes' B (stage II) and Dukes' C (stage III) carcinoma of the colon were entered onto National Surgical Adjuvant Breast and Bowl Project protocol C-04. Patients were randomly assigned to receive FU+LV (weekly regimen), FU + LEV, or the combination of FU+LV+LEV. The average time on study was 86 months. RESULTS: A pairwise comparison between patients treated with FU+LV or FU+LEV disclosed a prolongation in disease-free survival (DFS) in favor of the FU+LV group (65% v 60%; P = .04); there was a small prolongation in overall survival that was of borderline significance (74% v 70%; P = .07). There was no difference in the pairwise comparison between patients who received FU+LV or FU+LV+LEV for either DFS (65% v 64%; P = .67) or overall survival (74% v 73%; P = .99). There was no interaction between Dukes' stage and the effect of treatment. CONCLUSION: In patients with Dukes' B and C carcinoma of the colon, treatment with FU+LV seems to confer a small DFS advantage and a borderline prolongation in overall survival when compared with treatment with FU+LEV. The addition of LEV to FU+LV does not provide any additional benefit over and above that achieved with FU+LV. These findings support the use of adjuvant FU+LV as an acceptable therapeutic standard in patients with Dukes' B and C carcinoma of the colon.

The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03.

1993 ◽  
Vol 11 (10) ◽  
pp. 1879-1887 ◽  
Author(s):  
N Wolmark ◽  
H Rockette ◽  
B Fisher ◽  
D L Wickerham ◽  
C Redmond ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Therapy ◽  
Confidence Interval ◽  
Disease Free Survival ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Carcinoma Of The Colon ◽  
Bowel Project ◽  
To Receive ◽  
Disease Free

PURPOSE This study was designed to evaluate the efficacy of leucovorin-modulated fluorouracil (5-FU) as adjuvant therapy for patients with Dukes' stage B and C colon cancer. PATIENTS AND METHODS Data are presented from 1,081 patients with Dukes' stage B and C carcinoma of the colon entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) protocol C-03 between August 1987 and April 1989. Patients were randomly assigned to receive either lomustine (MeCCNU), vincristine, and 5-FU (MOF), or leucovorin-modulated 5-FU (LV + 5-FU). The mean time on study was 47.6 months. RESULTS Comparison between the two groups indicates a disease-free survival advantage for patients treated with LV + 5-FU (P = .0004). The 3-year disease-free survival rate for patients in this group was 73% (95% confidence interval, 69% to 77%), compared with 64% (95% confidence interval, 60% to 68%) for patients receiving MOF. The corresponding percentage of patients surviving was 84% for those randomized to receive LV + 5-FU and 77% for the MOF-treated cohort (P = .003). At 3 years of follow-up, patients treated with postoperative LV + 5-FU had a 30% reduction in the risk of developing a treatment failure and a 32% reduction in mortality risk compared with similar patients treated with MOF. CONCLUSION Treatment with LV + 5-FU significantly prolongs disease-free survival and results in a significant benefit relative to overall survival. These findings, when considered together with results from a recent meta-analysis demonstrating a benefit from LV + 5-FU in advanced disease, provide evidence to support the concept of metabolic modulation of 5-FU.

scholarly journals Bevacizumab in Stage II-III Colon Cancer: 5-Year Update of the National Surgical Adjuvant Breast and Bowel Project C-08 Trial

2013 ◽  
Vol 31 (3) ◽  
pp. 359-364 ◽  
Author(s):  
Carmen J. Allegra ◽  
Greg Yothers ◽  
Michael J. O'Connell ◽  
Saima Sharif ◽  
Nicholas J. Petrelli ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Disease Free Survival ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
End Point ◽  
Bowel Project ◽  
Modified Folfox6 ◽  
Disease Free

PurposeThe National Surgical Adjuvant Breast and Bowel Project trial C-08 was designed to investigate the safety and efficacy of adding bevacizumab to fluorouracil, leucovorin, and oxaliplatin (FOLFOX6) for the adjuvant treatment of patients with stage 2-3 colon cancer. Our report summarizes the primary and secondary end points of disease-free and overall survival, respectively, with 5 years median follow-up time.Patients and MethodsPatients received modified FOLFOX6 once every 2 weeks for a 6-month period (control group) or modified FOLFOX6 for 6 months plus bevacizumab (5 mg/kg) once every 2 weeks for a 12-month period (experimental group). The primary end point of the study was disease-free survival (DFS) and overall survival (OS) was a secondary end point.ResultsOf 2,673 analyzed patients, demographic factors were well-balanced by treatment. With a median follow-up of 5 years, the addition of bevacizumab to mFOLFOX6 did not result in an overall significant increase in DFS (hazard ratio [HR], 0.93; 95% CI, 0.81 to 1.08; P = .35). Exploratory analyses found that the effect of bevacizumab on DFS was different before and after a 1.25-year landmark (time-by-treatment interaction P value <.0001). The secondary end point of OS was no different between the two study arms for all patients (HR, 0.95; 95% CI, 0.79 to 1.13; P = .56) and for those with stage 3 disease (HR, 1.0; 95% CI, 0.83 to 1.21; P = .99).ConclusionBevacizumab for 1 year with modified FOLFOX6 does not significantly prolong DFS or OS in stage 2-3 colon cancer. We observed no evidence of a detrimental effect of exposure to bevacizumab. A transient effect on disease-free survival was observed during bevacizumab exposure in the study's experimental arm.

Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project Protocol C-02.

1990 ◽  
Vol 8 (9) ◽  
pp. 1466-1475 ◽  
Author(s):  
N Wolmark ◽  
H Rockette ◽  
D L Wickerham ◽  
B Fisher ◽  
C Redmond ◽  
...  
Keyword(s):  
Portal Vein ◽  
Treatment Failure ◽  
Hepatic Metastases ◽  
Disease Free Survival ◽  
Treated Group ◽  
Control Group ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Bowel Project ◽  
Disease Free

Between March 1984 and July 1988, 1,158 patients with Dukes' A, B, and C carcinoma of the colon were entered into National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol C-02. Patients were randomized to either no further treatment following curative resection or to postoperative fluorouracil (5-FU) and heparin administered via the portal vein. Therapy began on day of operation and consisted of constant infusion for 7 successive day. Average time on study was 41.8 months. A comparison between the two groups of patients indicated both an improvement in disease-free survival (74% v 64% at 4 years, overall P = .02) and a survival advantage (81% v 73% at 4 years, overall P = .07) in favor of the chemotherapy-treated group. When compared with the treated group, patients who received no further treatment had 1.26 times the risk of developing a treatment failure and 1.25 times the likelihood of dying after 4 years. Particularly significant was the failure to demonstrate an advantage from 5-FU in decreasing the incidence of hepatic metastases. The liver was the first site of treatment failure in 32.9% of 82 patients with documented recurrences in the control group and in 46.3% of 67 patients who received additional treatment. Therapy is administered via a regional route to affect the incidence of recurrence within the perfused anatomic boundary. Since, in this study, adjuvant portal-vein 5-FU infusion failed to reduce the incidence of hepatic metastases, it may be concluded that its use thus far is not justified. It may also be speculated that the disease-free survival and survival advantages (the latter of borderline significance) are a result of the systemic effects of 5-FU.

Two months of doxorubicin-cyclophosphamide with and without interval reinduction therapy compared with 6 months of cyclophosphamide, methotrexate, and fluorouracil in positive-node breast cancer patients with tamoxifen-nonresponsive tumors: results from the National Surgical Adjuvant Breast and Bowel Project B-15.

1990 ◽  
Vol 8 (9) ◽  
pp. 1483-1496 ◽  
Author(s):  
B Fisher ◽  
A M Brown ◽  
N V Dimitrov ◽  
R Poisson ◽  
C Redmond ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Positive Node ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Significant Difference ◽  
Bowel Project ◽  
Disease Free

The National Surgical Adjuvant Breast and Bowel Project (NSABP) implemented protocol B-15 to compare 2 months of Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) and cyclophosphamide (AC) with 6 months of conventional cyclophosphamide, methotrexate, and fluorouracil (CMF) in patients with breast cancer nonresponsive to tamoxifen (TAM, T). A second aim was to determine whether AC followed in 6 months by intravenous (IV) CMF was more effective than AC without reinduction therapy. Through 3 years of follow-up, findings from 2,194 patients indicate no significant difference in disease-free survival (DFS, P = .5), distant disease-free survival (DDFS, P = .5) or survival (S, P = .8) among the three groups. Since the outcome from AC and CMF was almost identical, the issue arises concerning which regimen is more appropriate for the treatment of breast cancer patients. AC seems preferable since, following total mastectomy, AC was completed on day 63 versus day 154 for conventional CMF; patients visited health professionals three times as often for conventional CMF as for AC; women on AC received therapy on each of 4 days versus on each of 84 days for conventional CMF; and nausea-control medication was given for about 84 days to conventional CMF patients versus for about 12 days to patients on AC. The difference in the amount of alopecia between the two treatment groups was less than anticipated. While alopecia was almost universally observed following AC therapy, 71% of the CMF patients also had hair loss and, in 41%, the loss was greater than 50%. This study and NSABP B-16, which evaluates the worth of AC therapy in TAM-responsive patients, indicate the merit of 2 months of AC therapy for all positive-node breast cancer patients.

Impact of Addition of Maintenance Therapy to Intensive Induction and Consolidation Chemotherapy for Childhood Acute Myeloblastic Leukemia: Results of a Prospective Randomized Trial, LAME 89/91

2002 ◽  
Vol 20 (12) ◽  
pp. 2774-2782 ◽  
Author(s):  
Yves Perel ◽  
Anne Auvrignon ◽  
Thierry Leblanc ◽  
Jean-Pierre Vannier ◽  
Gerard Michel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Low Dose ◽  
Disease Free Survival ◽  
High Dose ◽  
Induction Phase ◽  
Consolidation Therapy ◽  
Free Survival ◽  
Childhood Acute Myeloid Leukemia ◽  
To Receive

PURPOSE: To determine whether the use of maintenance therapy (MT) delivered after intensive induction and consolidation therapy confers any advantage in childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: A total of 268 children with AML were registered in the Leucámie Aiquë Myéloïde Enfant (LAME) 89/91 protocol. This regimen included an intensive induction phase (mitoxantrone plus cytarabine) and, for patients without allograft, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase, and amsacrine. In the LAME 89 pilot study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to receive or not receive MT. RESULTS: A total of 241 (90%) of 268 patients achieved a complete remission. The overall survival and event-free survival at 6 years were 60% ± 6% and 48% ± 6%, respectively. For the complete responders after consolidation therapy, the 5-year disease-free survival was not significantly different in MT-negative and in MT-positive randomized patients (respectively, 60% ± 19% v 50% ± 15%; P = .25), whereas the 5-year overall survival was significantly better in MT-negative randomized patients (81% ± 13% v 58% ± 15%; P = .04) due to a higher salvage rate after relapse. CONCLUSION: More than 50% of patients can be cured of AML in childhood. Either drug intensity or each of the induction and postremission phases may have contributed to the outstanding improvement in outcome. Low-dose MT is not recommended. Exposure to this low-dose MT may contribute to clinical drug resistance and treatment failure in patients who experience relapse.

Attempts to improve treatment outcomes in acute myeloid leukemia (AML) in older patients: the results of the United Kingdom Medical Research Council AML11 trial

Blood ◽  
2001 ◽  
Vol 98 (5) ◽  
pp. 1302-1311 ◽  
Author(s):  
Anthony H. Goldstone ◽  
Alan K. Burnett ◽  
Keith Wheatley ◽  
Alastair G. Smith ◽  
R. Michael Hutchinson ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Remission Rate ◽  
Disease Free Survival ◽  
Free Survival ◽  
To Receive ◽  
Disease Free ◽  
Acute Myeloid

In an attempt to improve induction chemotherapy for older patients with acute myeloid leukemia (AML),1314 patients were randomized to 1 of 3 induction treatments for 2 courses of DAT (daunorubicin, cytarabine, and thioguanine) 3 + 10, ADE (daunorubicin, cytarabine, and etoposide) 10 + 3 + 5, or MAC (mitoxantrone-cytarabine). The remission rate in the DAT arm was significantly better than ADE (62% vs 50%; P = .002) or MAC (62% vs 55%;P = .04). This benefit was seen in patients younger and older than 70 years. There were no differences between the induction schedules with respect to overall survival at 5 years (12% vs 8% vs 10%). A total of 226 patients were randomized to receive granulocyte colony-stimulating factor (G-CSF) or placebo as supportive care from day 8 after the end of treatment course 1. The remission rate or survival were not improved by G-CSF, although the median number of days to recover neutrophils to 1.0 × 109/L was reduced by 5 days. Patients who entered remission (n = 371) were randomized to stop after a third course (DAT 2 + 7) or after 6 courses, ie, a subsequent COAP (cyclophosphamide, vincristine, cytarabine, and prednisolone), DAT 2 + 5, and COAP. The relapse risk (81% vs 73%), disease-free survival (16% vs 23%), and overall survival at 5 years (23% vs 22%) did not differ between the 3-course or 6-course arms. In addition to a treatment duration randomization, 362 patients were randomized to receive 12-month maintenance treatment with low-dose interferon, but no benefit was seen with respect to relapse risk, disease-free survival, or overall survival.

Postoperative chemotherapy and tamoxifen compared with tamoxifen alone in the treatment of positive-node breast cancer patients aged 50 years and older with tumors responsive to tamoxifen: results from the National Surgical Adjuvant Breast and Bowel Project B-16.

1990 ◽  
Vol 8 (6) ◽  
pp. 1005-1018 ◽  
Author(s):  
B Fisher ◽  
C Redmond ◽  
S Legault-Poisson ◽  
N V Dimitrov ◽  
A M Brown ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Positive Node ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Bowel Project ◽  
Drug Regimens ◽  
Disease Free

The National Surgical Adjuvant Breast and Bowel Project (NSABP) conducted a randomized clinical trial to determine whether tamoxifen (TAM) plus chemotherapy is more effective than TAM alone in improving disease-free survival (DFS), distant disease-free survival (DDFS), and survival (S) of positive-node, TAM-responsive patients aged greater than or equal to 50 years. Women were randomized among three treatment groups: (1) TAM alone, (2) Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), cyclophosphamide, and TAM (ACT), or (3) melphalan (L-PAM), fluorouracil (5-FU), and TAM (PFT). The PFT arm was later modified so that new patients also received Adriamycin (PAFT). Findings from 1,124 eligible patients through 3 years of follow-up indicated a significantly better DFS for ACT-treated patients than for those receiving TAM alone (84% v 67%; P = .0004). An advantage in DDFS and S was also observed after ACT therapy (83% v 73% [P = .04 in the former] and 93% v 85% [P = .04 in the latter]). Both the DFS and DDFS of PAFT-treated patients were better than in those treated by TAM alone (83% v 66%, P = .0002 and 85% v 73%, P = .003). PFT patients also fared better in DFS and DDFS than TAM patients (81% v 72%, P = .07 and 85% v 74%, P = .02). Odds ratios consistently favored the three TAM-plus-chemotherapy groups. No significant S advantage is as yet evident in favor of the PAFT or PFT groups. Of importance is the failure of these studies to demonstrate an unfavorable interaction between the drug regimens used and the TAM, which was administered simultaneously. The findings related to the use of PAFT and PFT are of more biologic than clinical significance since L-PAM is rarely used in the treatment of breast cancer. The major conclusion from this study is the observance of a better outcome in positive-node breast cancer patients aged greater than or equal to 50 years from the use of postoperative prolonged TAM and short-course AC therapy (completed in 63 days) than from prolonged TAM therapy alone.

Comparative Efficacy of Adjuvant Chemotherapy in Patients With Dukes' B Versus Dukes' C Colon Cancer: Results From Four National Surgical Adjuvant Breast and Bowel Project Adjuvant Studies (C-01, C-02, C-03, and C-04)

1999 ◽  
Vol 17 (5) ◽  
pp. 1349-1349 ◽  
Author(s):  
Eleftherios Mamounas ◽  
Samuel Wieand ◽  
Norman Wolmark ◽  
Harry D. Bear ◽  
James N. Atkins ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Prognostic Factors ◽  
Adjuvant Chemotherapy ◽  
Relative Efficacy ◽  
Mortality Reduction ◽  
Free Survival ◽  
National Surgical Adjuvant Breast ◽  
Bowel Project ◽  
Disease Free ◽  
Dukes C

PURPOSE: Although the benefit from adjuvant chemotherapy has been clearly established in patients with Dukes' C colon cancer, such benefit has been questioned in patients with Dukes' B disease. To determine whether patients with Dukes' B disease benefit from adjuvant chemotherapy and to evaluate the magnitude of the benefit, compared with that observed in Dukes' C patients, we examined the relative efficacy of adjuvant chemotherapy according to Dukes' stage in four sequential National Surgical Adjuvant Breast and Bowel Project trials (C-01, C-02, C-03, and C-04) that compared different adjuvant chemotherapy regimens with each other or with no adjuvant treatment. PATIENTS AND METHODS: The four trials included Dukes' B and C patients and were conducted between 1977 and 1990. The eligibility criteria and follow-up requirements were similar for all four trials. Protocol C-01 compared adjuvant semustine, vincristine, and fluorouracil (5-FU) (MOF regimen) with operation alone. Protocol C-02 compared the perioperative administration of a portal venous infusion of 5-FU with operation alone. Protocol C-03 compared adjuvant 5-FU and leucovorin (LV) with adjuvant MOF. Protocol C-04 compared adjuvant 5-FU and LV with 5-FU and levamisole (LEV) and with the combination of 5-FU, LV, and LEV. RESULTS: Forty-one percent of the patients included in these four trials had resected Dukes' B tumors. In all four studies, the overall, disease-free, and recurrence-free survival improvement noted for all patients was evident in both Dukes' B and Dukes' C patients. When the relative efficacy of chemotherapy was examined, there was always an observed reduction in mortality, recurrence, or disease-free survival event, irrespective of Dukes' stage, and in most instances, the reduction was as great or greater for Dukes' B patients as for Dukes' C patients. When data from all four trials were examined in a combined analysis, the mortality reduction was 30% for Dukes' B patients versus 18% for Dukes' C patients. The mortality reduction in Dukes' B patients occurred irrespective of the presence or absence of adverse prognostic factors. CONCLUSION: Patients with Dukes' B colon cancer benefit from adjuvant chemotherapy and should be presented with this treatment option. Regardless of the presence or absence of other clinical prognostic factors, Dukes' B patients seem to benefit from chemotherapy administration.

LOPP alternating with EVAP is superior to LOPP alone in the initial treatment of advanced Hodgkin's disease: results of a British National Lymphoma Investigation trial.

1992 ◽  
Vol 10 (8) ◽  
pp. 1252-1258 ◽  
Author(s):  
B W Hancock ◽  
G Vaughan Hudson ◽  
B Vaughan Hudson ◽  
M H Bennett ◽  
K A MacLennan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin's Disease ◽  
Initial Treatment ◽  
Hodgkin’S Disease ◽  
Disease Free Survival ◽  
Free Survival ◽  
Residual Masses ◽  
To Receive ◽  
Free Rate ◽  
Advanced Hodgkin’S Disease

PURPOSE The purpose of this randomized trial was to compare the efficacy of eight cycles of chlorambucil, vincristine, procarbazine, and prednisone (LOPP) with four cycles of LOPP that alternate with four cycles of etoposide, vinblastine, Adriamycin (doxorubicin; Familitalia Carlo Erba, Ltd, UK), and prednisone (EVAP) in patients with advanced Hodgkin's disease. PATIENTS AND METHODS Between June 1983 and December 1989, 594 patients were entered onto the study. Of the 594, 295 patients were allocated to receive LOPP, and 299 were allocated to receive LOPP/EVAP. RESULTS The complete remission (CR) rates were 57% and 64%, respectively, after initial chemotherapy (difference not significant [NS]), and 65% and 75%, respectively, after the subsequent administration of radiotherapy to residual masses (P less than .01). The procedure associated mortality in the LOPP and LOPP/EVAP arms was 1% and 3%, respectively. The actuarial CR relapse-free survival was significantly greater in the LOPP/EVAP arm (P less than .001) as was the overall survival (P less than .05). The CR relapse-free rate, disease-free survival (DFS) rate, and overall survival rate at 5 years were 52%, 32%, and 66%, respectively, in the LOPP arm, compared with 72%, 47%, and 75% in the LOPP/EVAP arm, respectively. CONCLUSION These results indicate that LOPP and EVAP is superior to LOPP alone as initial treatment for advanced Hodgkin's disease.

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