H. C. Falkson

Locoregional Failure 10 Years After Mastectomy and Adjuvant Chemotherapy With or Without Tamoxifen Without Irradiation: Experience of the Eastern Cooperative Oncology Group

PURPOSE To assess patterns of failure and how selected prognostic and treatment factors affect the risks of locoregional failure (LRF) after mastectomy in breast cancer patients with histologically involved axillary nodes treated with chemotherapy with or without tamoxifen without irradiation. PATIENTS AND METHODS The study population consisted of 2,016 patients entered onto four randomized trials conducted by the Eastern Cooperative Oncology Group. The median follow-up time for patients without recurrence was 12.1 years (range, 0.07 to 19.1 years). RESULTS A total of 1,099 patients (55%) experienced disease recurrence. The first sites of failure were as follows: isolated LRF, 254 (13%); LRF with simultaneous distant failure (DF), 166 (8%); and distant only, 679 (34%). The risk of LRF with or without simultaneous DF at 10 years was 12.9% in patients with one to three positive nodes and 28.7% for patients with four or more positive nodes. Multivariate analysis showed that increasing tumor size, increasing numbers of involved nodes, negative estrogen receptor protein status, and decreasing number of nodes examined were significant for increasing the rate of LRF with or without simultaneous DF. CONCLUSION LRF after mastectomy is a substantial clinical problem, despite the use of chemotherapy with or without tamoxifen. Prospective randomized trials will be necessary to estimate accurately the potential disease-free and overall survival benefits of postmastectomy radiotherapy for patients in particular prognostic subgroups treated with presently used and future systemic therapy regimens.

A clinical trial of the oral form of 4′-demethyl-epipodophyllotoxin-β-D ethylidene glucoside (NSC 141540) VP 16–213†

A clinical trial of the oral form of VP 16‐213 (NSC‐141540), a semisynthetic podophyllotoxin, was undertaken. In 20 patients, treatment was started at 200 mg/day p.o. for 5 days; courses were repeated after a rest period of 16 days. Five patients were treated at the same dose, repeated with only 9‐day rest periods. Subsequently, 65 patients were given 300–400 mg/day for 5 days, with rest periods of 9 days between courses. The side effects encountered included anorexia, nausea and vomiting, stomatitis, diarrhea, leukopenia, throm‐bocytopenia, alopecia, and pruritis. Substernal discomfort with or without palpitations was reported by 18 patients; no explanation for this symptom could be found. No complete remissions (CR) were observed. Partial remissions (PR) and improvement (IMP) were seen as follows: small cell carcinoma, lung (10 patients)—2 PR, 3 IMP; adenocarcinoma, lung (4 patients)—1 PR; alveolar cell carcinoma, lung (1 patient)—1 IMP; mesothelioma (4 patients)—1 IMP; ovarian cancer (12 patients)—3 PR, 3 IMP; breast cancer (20 patients)—4 IMP; colon cancer (8 patients)—2 IMP; bladder cancer (4 patients)—2 IMP; histiocytic lymphoma (7 patients)—2 PR, 3 IMP; chronic myeloid leukemia (1 patient)—1 IMP.

A randomized trial of five and three drug chemotherapy and chemoimmunotherapy in women with operable node positive breast cancer.

Women with breast carcinoma and four or more involved ipsilateral axillary lymph nodes were randomly assigned to receive an induction course and 2 yr of maintenance chemotherapy with cyclophosphamide, methotrexate and 5-fluorouracil (CMF, 150 patients), CMF plus vincristine and prednisone (CMFVP, 166 patients), or chemoimmunotherapy with CMF plus the methanol extraction residue of BCG (CMF-MER, 85 patients). After 5 yr of accrual and a median follow-up of 34 mo, CMFVP is superior to CMF (p less than 0.01) with disease-free survival estimates at 4 yr of 60% for CMFVP compared to 45% for CMF. The disease-free survival advantage of CMFVP over CMF was greater in postmenopausal (p = 0.02) than in premenopausal patients (p = 0.09). CMF-MER was similar to CMF alone. CMF related side effects were similar in each regimen (see text), except for a greater incidence of leukopenia during induction with CMF than with CMFVP (p less than 0.01).

Adjuvant trial of 12 cycles of CMFPT followed by observation or continuous tamoxifen versus four cycles of CMFPT in postmenopausal women with breast cancer: an Eastern Cooperative Oncology Group phase III study.

A prospectively controlled randomized trial to compare the adjuvant efficacy of 12 cycles of cyclophosphamide, methotrexate, fluorouracil, prednisone, and tamoxifen (CMFPT) followed by observation or a total of 5 years of continuous tamoxifen versus four cycles of CMFPT followed by observation in postmenopausal women with operable node-positive breast cancer was started by the Eastern Cooperative Oncology Group (ECOG) in 1982. In 1986 the study was modified to allow patients on CMFPT X 12 plus continuous tamoxifen to be rerandomized after completing 5 years of tamoxifen to either continue for life or to stop therapy. Patients were stratified for number of involved nodes and estrogen-receptor (ER) status and randomized to receive one of three treatments: CMFPT X 4, CMFPT X 12, or CMFPT X 12 plus continuous tamoxifen. Of 962 patients entered on the study, 803 were eligible. Life-threatening toxicity occurred in 75 and lethal toxicity in seven patients. Median follow-up is 4.1 years; 279 patients had recurrent disease. Time to relapse (TTR) is significantly longer for patients on CMFPT X 12 plus continuous tamoxifen than for CMFPT X 4 (P = .002), or CMFPT X 12 (P = 0.05). Differences between four or 12 cycles of CMFPT are not significant; relapse-free rates at 5 years are 61% for CMFPT X 12 plus continuous tamoxifen, 51% on CMFPT X 12, and 52% on CMFPT X 4. Treatment differences in overall survival are not significant. Hormone receptor status and number of involved nodes were found to be significant prognostic parameters.

Non-Hodgkin's lymphoma in pregnancy.

Non‐Hodgkins lymphoma associated with pregnancy is rare. To date, only 1 case in which lymphoma was diagnosed and treated during pregnancy, with normal pregnancy outcome, has been reported. We describe another case where life‐threatening, diffuse, poorly differentiated lymphocytic lymphoma was diagnosed during the 13th week of pregnancy. Combination chemotherapy (cyclophosphamide, vincristine, bleomycin, and prednisone) resulted in remission and a healthy full‐term infant was born.

Improved remission rates and remission duration in young women with metastatic breast cancer following combined oophorectomy and chemotherapy. A study by cancer and leukemia group B

One hundred fifty‐seven premenopausal women with metastatic breast cancer were prospectively randomized to treatment consisting of oophorectomy + vincristine, prednisone, cyclophosphamide, methotrexate, 5‐fluorouracil (VPCMF) (Reg. I) or oophorectomy + cyclophosphamide (Reg. II) or oophorectomy followed by an observation period (Phase 1), followed by VPCMF (Phase 2) (Reg. III). Complete plus partial response rates were 72% on Reg. I, 65% on Reg. II, 18% on Reg. III, Phase 1 and 50% on Reg. III, Phase 2. Median duration of response for Reg. I was 17 months, for Reg. II 16 months, and for Phase 1 and Phase 2 of Reg. III, respectively, 5 months and 8 months. The response rate for patients treated with oophorectomy plus chemotherapy is significantly higher than the response rate achieved with oophorectomy alone as first treatment following the appearance of metastases in premenopausal women.

Carcinoembryonic antigen in patients with breast cancer. An adjunctive tool to monitor response and therapy

Plasma carcinoembryonic antigen (CEA) levels were performed by radioimmunoassay in 234 patients with histologically proved breast cancer: 181 with advanced metastatic disease and 53 without distant metastases but nodal involvement at time of mastectomy. Four hundred and thirty‐four assays were done and correlated with the clinical status of the patients. Values above 2.5 ng/ml were taken as abnormal. Active disease was associated with elevated plasma CEA levels. Very high values were not recorded in 109 patients when they were considered to be in complete remission, while only 22 patients out of 63 patients with progressive disease had normal values. In 16 of these, values remained normal despite progression of disease. In 6 patients clinical relapse preceded CEA elevation by 2–5 months. Tumor burden and abnormal serial CEA values showed positive correlation in 38 patients. In 30 patients, change in clinical status and CEA values occurred simultaneously. In only 2 patients an increase in CEA value occurred 2–3 months before clinical documentation of relapse.

Mesnum as a Protector Against Kidney and Bladder Toxicity with High-Dose Ifosfamide Treatment

SummaryThirty-two patients with advanced cancer were treated in a phase I–II trial with ifosfamide plus mesnum. At doses up to 300 mg ifosfamide/kg the administration of mesnum prevented most of the expected kidney and bladder toxicity. With this high dose range hemopoietic dose-limiting. Only one of twelve evaluable patients with breast cancer showed definite therapeutic benefit. Complete remission or partial remission was seen in three patients with non-Hodgkin lymphoma and one patient with Hodgkins disease.

Combination of dacarbazine, mitomycin C, 5-fluorouracil and vincristine in advanced colorectal cancer.

SummaryThirty patients with advanced measurable colorectal cancer received monthly courses of a combination of dacarbazine, mitomycin C, 5-fluorouracil, and vincristine (FIV Mit-Or). Four of the patients had received prior chemotherapy. Two patients were not evaluable for response. Objective response was obtained in four patients. Severe toxicity was encountered in 11 patients. It is concluded that unlike the fourdrug combination of 5-fluorouracil, DTIC, vincristine and BCNU (FIVB), the present regimen did not have significant antitumour activity in advanced colorectal cancer.