Fluoxymesterone-induced gynaecomastia in a patient with childhood aplastic anaemia.

Gynaecomastia is a benign condition characterised by enlargement of the male breast. Drug-induced gynaecomastia merits deep consideration as it may account for as many as 25% of all cases of gynaecomastia in adults. Although the mechanism is not fully clear, some mechanisms include oestrogen-like activities, stimulation of testicular production of oestrogens, inhibition of testosterone synthesis or blockade of androgen action. Anabolic steroids, in particular when used during the pubertal stage, may cause significant irreversible gynaecomastia. We report a case of 28-year-old Filipino man with persistent gynaecomastia from fluoxymesterone used for aplastic anaemia during his prepubertal stage. Hormonal work ups for gynaecomastia all turned out normal, thus isolating the drug as the cause. The patient was unable to undergo breast reconstruction surgery due to haematological contraindications, but eventually referred to psychiatry for counselling. This case will highlight the paradoxical effect of androgenic steroid used during childhood on male breast proliferation during puberty.

Mini-dose of thalidomide for treatment of primary myelofibrosis. Report of a case with complete reversal of bone marrow fibrosis and splenomegaly.

We report a patient with very advanced myelofibrosis and huge splenomegaly who showed a complete hematological response to low dose thalidomide with reversal of splenomegaly and bone narrow fibrosis after 30 months of the treatment.

Randomized trial of tamoxifen alone or combined with fluoxymesterone as adjuvant therapy in postmenopausal women with resected estrogen receptor positive breast cancer. North Central Cancer Treatment Group Trial 89-30-52.

PURPOSE: This clinical trial evaluated the addition of fluoxymesterone (Flu) to tamoxifen (Tam) in women with resected early stage breast cancer and attempted to corroborate the findings of superiority for the combination over Tam alone seen in a previous randomized trial in metastatic disease. PATIENTS AND METHODS: Postmenopausal women with early stage breast cancer that was known to be estrogen receptor (ER) positive were randomized to treatment with Tam (20 mg per day orally for 5 years) alone or combined with Flu (10 mg orally twice per day for 1 year). The primary endpoint was relapse-free survival (RFS) defined as local-regional or distant recurrence including ductal carcinoma in situ of the ipsilateral, but not contralateral breast, and death from any cause. RESULTS: There were 541 eligible patients entered between 1991 and 1995 and the treatment arms were balanced with respect to patient characteristics. The median follow up of patients still alive was 11.4 years. No significant difference was found between Tam plus Flu and Tam alone in terms of RFS or overall survival. The adjusted hazard ratio (Tam+Flu/Tam) for relapse or death without relapse was estimated to be 0.84 (95% CI: 0.64-1.10) and that for death was 0.89 (95% CI: 0.67-1.18). As expected there was more virilization in women who received Flu. CONCLUSIONS: This clinical trial did not demonstrate superiority of Tam plus Flu over Tam alone as adjuvant therapy for postmenopausal women with resected early breast cancer known to be ER positive.

Combined endocrine treatment of elderly postmenopausal patients with metastatic breast cancer. A randomized trial of tamoxifen vs. tamoxifen + aminoglutethimide and hydrocortisone and tamoxifen + fluoxymesterone in women above 65 years of age.

The efficacy of combined endocrine therapy with tamoxifen (TAM), aminoglutethimide (AG), and hydrocortisone (H) or tamoxifen and fluoxymesterone (FLU) was evaluated against treatment with tamoxifen alone in 311 patients above 65 years of age with a first recurrence of a metastatic breast cancer. A total of 279 patients were eligible. The response rates were assessed for 258 fully evaluable patients and were the following for the TAM (N = 94), the TAM+AG+H (N = 83), and the TAM+FLU (N = 81) groups, respectively, PR: 14, 18, and 21%, and CR: 20, 11, and 23%. The overall response rates are not statistically different (p = 0.30). The 95% CL of difference in response rates for TAM vs. TAM+AG+H are -9-19% and for TAM vs. TAM+FLU -4-25%. Time to treatment failure was comparable with median values of 9.2, 7.7, and 9.2 months in the TAM, TAM+AG+H, and TAM + FLU group, respectively (p = 0.17). The corresponding figures for survival are median times of 22.0, 24.1, and 21.1 months with a p-value of 0.62. Toxicity was more pronounced in both the combined treatment groups, and could in most instances be attributed to treatment with either AG+H or FLU. Currently, new specific aromatase inhibitors with lesser toxicity than AG are being evaluated in combination with TAM for treatment of primary and metastatic breast cancer. In conclusion, the simultaneous use of TAM and AG +H or FLU does not seem to improve the therapeutic efficacy in elderly postmenopausal patients with metastatic disease. So far, combined endocrine therapy in this group of patients should only be used in the context of clinical trials.

Comparison of chemotherapy with chemohormonal therapy as first-line therapy for metastatic, hormone-sensitive breast cancer: An Eastern Cooperative Oncology Group study.

PURPOSE: Although hormonal therapy represents standard therapy for metastatic hormone-sensitive disease, many patients receive initial chemotherapy because of the location, bulk, or aggressiveness of their disease. It is uncertain whether simultaneous hormonal therapy provides additional benefit compared with chemotherapy alone. Eastern Cooperative Oncology Group trial E3186 was initiated to explore this question. PATIENTS AND METHODS: Between January 1988 and December 1992, 231 patients with estrogen receptor (ER)-positive or ER-unknown metastatic breast cancer were randomized to receive either chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil ¿CAF) or chemohormonal therapy (CAF plus tamoxifen and Halotestin ¿fluoxymesterone; Pharmacia-Upjohn, Kalamazoo, MI ¿CAFTH) as front-line therapy for metastatic breast cancer. Patients who experienced a complete response to induction therapy either received or did not receive maintenance cyclophosphamide, methotrexate, fluorouracil, prednisone, and TH as a secondary randomization. RESULTS: The response rates (complete response and partial response) of patients who received CAF and CAFTH were similar (69.2% v 68.9%, respectively; P =.99). Time to treatment failure (TTF) was slightly longer for patients who received chemohormonal therapy compared with chemotherapy alone patients (13.4 months v 10.3 months, respectively; P =.087), and TTF was significantly longer in ER-positive compared with ER-negative patients (17.4 months v 10.3 months, respectively; P =.048). However, ER status had no effect on overall survival (30.0 months for CAF v 29.3 months for CAFTH). CONCLUSION: In patients with potentially hormone-sensitive metastatic breast cancer, chemohormonal therapy prolongs TTF for ER-positive patients without improving overall survival.

Eastern Cooperative Oncology Group randomized trials of observation versus maintenance therapy for patients with metastatic breast cancer in complete remission following induction treatment.

PURPOSE: To investigate the value of maintenance treatment for patients with metastatic breast cancer whose disease is in complete remission (CR). PATIENTS AND METHODS: One hundred ninety-five women (141 eligible) whose disease was in CR or in CR except for bone metastases following six cycles (6 months) of doxorubicin-containing induction treatment were randomized to receive cyclophosphamide, methotrexate, fluorouracil, prednisone, tamoxifen, and halotestin [CMF(P)TH] or observation. In a previous pilot study, patients in CR after 24 months of induction treatment were randomized to continue chemotherapy for 4 more years or stop chemotherapy. RESULTS: Among patients randomized to CMF(P)TH, life-threatening toxicity included leukopenia in 3%, thrombocytopenia in 3%, cardiac in 2%, and diabetes in 1%. The median time to relapse from randomization was 18.7 months on CMF(P)TH and only 7.8 months on observation (P < .0001). The median time to death was 32.2 months on CMF(P)TH and 28.7 months on observation (P=.74). Similar results were seen in the pilot study (median time to relapse, 12.6 and 6.4 months; median survival, 37.7 and 24.2 months; study too small for statistical significance). Maintenance treatment was always the most significant covariate in time-to-relapse models. CONCLUSION: There is definite toxicity associated with CMF(P)TH maintenance treatment. When CR was obtained on induction, maintenance treatment with CMF(P)TH was never significant in survival models. However, maintenance treatment was always the most significant covariate in the time-to-relapse models, which motivates its consideration for appropriately informed patients.

Induction chemotherapy of dibromodulcitol, Adriamycin, vincristine, tamoxifen, and Halotestin with methotrexate in metastatic breast cancer: an Eastern Cooperative Oncology Group Study (E1181).

Patients who have metastatic breast cancer are seldom curable. Chemotherapy given by conventional doses and schedules generally produces complete remissions in 10% to 20% of patients. This study sought to determine 1) whether a combination of dibromodulcitol, Adriamycin, vincristine, tamoxifen, Halotestin, and methotrexate with leucovorin rescue (DAVTHML) can produce a complete remission rate of 50%; and 2) the toxicity of this combination in patients with chemotherapy-naive metastatic breast cancer. Patients were treated with six 28-day cycles of DAVTHML induction chemotherapy consisting of dibromodulcitol, 135 mg/m2 perorally days 1 to 10; Adriamycin 45 mg/m2 intravenously day 1; vincristine, 2 mg intravenously day 1; tamoxifen and Halotestin, 20 mg perorally daily; methotrexate, 800 mg/m2 intravenously days 15 and 22; and leucovorin, 15 mg/m2 perorally every 6 hours for 9 doses, starting 4 hours after methotrexate. After induction, patients who had stable disease or a partial response were treated with a cyclophosphamide, methotrexate, and 5-fluorouracil-based regimen (CMF). Patients in complete remission were treated with three additional cycles of DAVTHML after achieving complete remission and then observed off therapy until relapse, when DAVTHML was to be given again. Fifty-eight patients were included in this study. During induction, 26% of eligible patients experienced a complete remission; overall response rate was 80%. The median time to treatment failure and the median survival time of eligible patients was 11.1 and 24.0 months, respectively. This did not change significantly when all the patients were included in the evaluation. The 3-year and 5-year survival rates were 37% and 11%, respectively. Ninety percent of the eligible patients experienced grade III or IV toxicity. They were leukopenia (75%), anemia (20%), thrombocytopenia (20%), and vomiting (17%). No lethal toxicity was documented during therapy; however, 1 patient later died of myelodysplastic syndrome induced by dibromodulcitol. The overall response and complete remission rates from our study were encouraging. The toxicity of DAVTHML was tolerable, with the exception of myelodysplastic syndrome from dibromodulcitol. The concept of using mid-cycle nonmyelosuppressant agents to increase complete remission rate is feasible.

Amenorrhea induced by adjuvant chemotherapy in early breast cancer patients: prognostic role and clinical implications.

BACKGROUND: The role of amenorrhea induced by chemotherapy in premenopausal women with early breast cancer is very controversial. Analyses by various authors of the effect of drug-induced amenorrhea (DIA) on treatment outcome have yielded conflicting results. In order to gain insight into the role of DIA, we reviewed all published data addressing the issue of DIA as a prognostic factor. METHODS: Computerised and manual searches were conducted of relevant studies published from 1966 to 1995. RESULTS: Thirteen studies involving 3929 patients were selected. In two papers, the prognostic role of DIA was analysed in three and two different groups of patients, respectively. Overall, 16 groups of patients were evaluated. With 12 groups, a higher disease free survival was observed in patients developing DIA compared to those who did not. This difference was statistically significant in eight groups. Data on overall survival, reported in only five studies, indicated that it was always improved in patients who became amenorrheic. CONCLUSIONS: Available data on the role of DIA support its importance as a favorable prognostic factor for early breast cancer patients. However, due to the possible biases of this type of evaluation, this result should be interpreted with caution.

The role of radiotherapy in the management of operable locally advanced breast carcinoma: results of a randomized trial by the Eastern Cooperative Oncology Group.

BACKGROUND: The purpose of this study was to test the role of radiotherapy following total mastectomy, axillary dissection, and adjuvant systemic therapy in the management of operable locally advanced breast carcinoma. METHODS: After undergoing mastectomy and axillary dissection, 426 patients with locally advanced breast carcinoma were registered on study and stratified by patient characteristics and risk factors. All patients were then treated with six courses of chemohormonotherapy. After being restaged, the 332 patients remaining without recurrence were randomized to receive prophylactic radiotherapy or to undergo observation and receive radiotherapy only if and when there was locoregional recurrence. RESULTS: Three hundred twelve of 332 randomized patients were deemed eligible and analyzed for both time to relapse and survival. The median follow-up period was 9.1 years. There were no significant differences in time to relapse and overall survival between the two treatment arms. Of those assigned to radiation, 60% relapsed, with a median time to relapse of 4.7 years, and 46% were alive at last follow-up, with a median survival of 8.3 years. Of those assigned to observation, 56% relapsed, with a median time to relapse of 5.2 years, and 47% were alive at last follow-up, with a median survival of 8.1 years. The two treatment arms had significantly different patterns of sites of first recurrence. There were 9% fewer locoregional first recurrences among those assigned to radiation than among those assigned to observation (15% vs. 24%), whereas there were 15% more first relapses at distant sites (50% vs. 35%) among those assigned to radiation (P = 0.003). CONCLUSIONS: Radiotherapy for locally advanced breast carcinoma, following mastectomy, axillary dissection, and adjuvant systemic therapy, results in fewer locoregional but more distant recurrences at first relapse. No significant advantage was seen for consolidation radiotherapy over observation in terms of either time to relapse or survival, both of which were virtually identical in the two treatment arms. [See editorial counterpoint on pages 1061-6 and reply to counterpoint on pages 1067-8, this issue.]

Postsurgical adjuvant chemotherapy of stage II breast carcinoma with or without crossover to a non-cross-resistant regimen: a Cancer and Leukemia Group B study.

PURPOSE: To compare two cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) regimens with a doxorubicin-based regimen--vinblastine, doxorubicin, thiotepa, and Halotestin (Upjohn, Kalamazoo, MI) (VATH)--in patients with stage II node-positive breast carcinoma. METHODS: Nine hundred forty-five women were treated with a 6-week induction course of CMFVP. They were then randomized to receive one of two consolidation CMFVP regimens: 6-week courses or 2-week courses. Following completion of CMFVP consolidation, patients were again randomized to either continue the CMFVP regimen or to receive six escalating doses of VATH. RESULTS: Among all patients, with a median follow-up time of 11.5 years, there is no statistically significant difference in disease-free survival (DFS) between the two consolidation CMFVP regimens. VATH intensification treatment is statistically significantly superior to CMFVP in terms of DFS (P = .0040). For patients with one to three involved nodes, there is currently no significant difference between VATH and CMFVP; however, among those with four or more positive lymph nodes, there is a significant difference in favor of VATH (P = .0037). There is also improved overall survival with VATH (P = .043; median, > 14 years v 10 years). This difference is also statistically significant in patients with four or more involved lymph nodes, among postmenopausal patients, and among postmenopausal estrogen receptor-positive patients. CONCLUSION: Chemotherapy with crossover to escalating doses of VATH following CMFVP was well tolerated and effective. Inauguration of VATH as a treatment intensification at the eighth month produced a major increase in relapse-free and overall survival. The observation that sensitivity to VATH is retained so long after mastectomy raises questions about the proper duration of adjuvant chemotherapy and lends support to further investigation of cross-over designs in future trials to postoperative adjuvant chemotherapy regimens.

Combination chemotherapy for metastatic or recurrent carcinoma of the breast--a randomized phase III trial comparing CAF versus VATH versus VATH alternating with CMFVP: Cancer and Leukemia Group B Study 8281.

PURPOSE: We sought to compare three doxorubicin-based therapies for metastatic breast cancer for response frequency, time to treatment failure (TTF), and survival. MATERIALS AND METHODS: Women with metastatic breast cancer who had measurable disease, required laboratory tests, had received no prior chemotherapy for metastases, had a Cancer and Leukemia Group B (CALGB) performance status < or = 2, and provided informed consent were eligible. Treatment included the following: arm I--cyclophosphamide, doxorubicin, and fluorouracil (CAF); arm II--vinblastine, doxorubicin, thiotepa, and halotestin (VATH); and arm III--VATH alternating with cyclophosphamide, methotrexate, fluorouracil, vincristine, and prednisone (CMFVP) on cycles 3, 5, 7, 9, etc. Doses were modified for toxicities. Standard CALGB response and toxicity criteria were used. RESULTS: Between August 1982 and February 1987, 497 women were entered and 491 were treated on study. Pretreatment characteristics were well balanced and the median follow-up duration was 79 months. There were no significant differences in response (complete [CR] plus partial [PR]) at 50% on arm I, 57% on arm II, and 51% on arm III. The median TTFs were 8, 8, and 9 months, respectively, in favor of arm III when compared with arm I (P = .028). The median survival times for treatment arms I, II, and III were 15, 17, and 17 months, respectively. After multivariate regression analyses, only estrogen receptors (ER), performance status, and number of metastatic sites influenced TTF and survival. Leukopenia was the most common grade 3 or 4 toxicity, occurring in 90%, 80%, and 92% of patients per arm, respectively. Lethal toxicities were seen in four, five, and six women, respectively. Overall, there were more grade > or = 3 toxicities on arm II than I, and most occurred on arm III (P = .02). CONCLUSION: The VATH regimen appears similarly effective to the CAF regimen as initial therapy. Alternating CMFVP with VATH did not improve response rate or survival. After accounting for other variables, treatment arm was not related to outcome. New therapeutic regimens are still needed.

Adult height in girls with Turner syndrome treated with low-dose estrogens and androgens.

OBJECTIVE: To determine if low dosages of estrogens and androgens administered to girls with Turner syndrome adversely affected their adult height. DESIGN: A nonrandomized control trial of nine girls. SETTING: The endocrine clinic at Texas Children's Hospital in Houston, Texas, an academic referral center. PARTICIPANTS: Participants had chromosomal defects consistent with Turner syndrome. Informed consent was obtained in accordance with institutional review board procedures. Eligibility criteria included an absence of previous hormone treatment. No one withdrew from this study because of adverse effects. INTERVENTIONS: Hormonal replacement therapy was initiated with conjugated estrogen 0.15 mg and fluoxymesterone 1 mg administered daily. MAIN OUTCOME MEASURES: Outcome measurements were a comparison of the final heights following treatment versus the predicted adult heights prior to treatment. RESULTS: The predicted adult height in these children prior to treatment was 140.0 +/- 4.4 cm (mean +/- SD); the actual adult height was 139.63 +/- 4.1 cm. The difference was 0.37 +/- 3.54 cm, which was not statistically significant by Wilcoxon signed-rank test (p = 0.23). The 95% confidence interval on this difference ranged from -3.1 to 2.3 cm, which indicates a true mean height loss of no more than 3.1 cm or a true mean gain of no more than 2.3 cm. CONCLUSIONS: Our results indicate that hormone replacement therapy with low dosages of conjugated estrogens and androgens starting at 10-11 years of age in children with Turner syndrome does not adversely affect actual adult height.

Reinduction with the same cytostatic treatment in patients with metastatic breast cancer: an Eastern Cooperative Oncology Group study.

PURPOSE: To investigate the therapeutic value of reinduction with the same cytostatic treatment that had been used in induction treatment for women with metastatic breast cancer. MATERIALS AND METHODS: One hundred six women with metastatic breast cancer were given dibromodulcitol (mitolactol), doxorubicin, vincristine, tamoxifen, and fluoxymesterone (DAVTH) for 6 months of induction treatment, then randomized to receive one of two chemotherapy regimens if they had obtained an induction partial response (PR) or no change (NC), or to receive observation versus chemotherapy if they had obtained an induction complete response (CR). Patients were then retreated with DAVTH reinduction after relapse. RESULTS: Seventy-four patients were eligible or had minor reasons for ineligibility. Severe or life-threatening toxicity was documented in 46%, and lethal toxicity in 4%. Eighteen percent had a response on reinduction (zero of 16 induction nonresponders, 15% induction PR, 44% induction CR). The median time to treatment failure (TTF) from reinduction was 3 months, and the median survival duration from reinduction was 14 months. In a logistic model, factors associated with more reinduction responses were observation after induction CR (P = .002) and age greater than 55 years (P = .04). Time since induction was not significant. CONCLUSION: Reinduction of response after treatment failure remains a therapeutic problem. The need for better salvage treatment underlines the importance of developing new regimens.

Long-term results of treatment with low-dose fluoxymesterone in constitutional delay of growth and puberty and in genetic short stature.

This prospective study was designed to assess growth response, side effects, other possible long-term effects, and final adult height in boys treated with the oral androgen, fluoxymesterone. From 1973 to 1984, eighty-two short boys (71 with constitutional delay of growth and puberty [CDGP] and 11 with genetic short stature [GSS]) were treated with daily oral doses of 2.5 mg of fluoxymesterone from 6 to 60 months. Final height assessment was made from 1989 to 1991. A group of 34 untreated boys (26 with CDGP and 8 with GSS) were also followed to assess the accuracy of the Greulich-Pyle and Bayley-Pinneau (GP-BP) and sexual maturity index height prediction methods. During treatment, each patient had a 1.7- to 2.5-fold increase in linear growth velocity. Accelerated velocity (over baseline) continued as long as the bone age was less than 14 years. No adverse androgenic effects (or undue acceleration of puberty) were observed. Final height exceeded pretreatment predictions for CDGP + GSS by 6.1 +/- 3.5 (SD) cm (GP-BP) and 5.4 +/- 3.2 cm (sexual maturity index). It is concluded that a daily oral dose of 2.5 mg of fluoxymesterone can be used to accelerate linear growth in boys with CDGP and GSS when needed to alleviate emotional problems secondary to slow growth and short stature without fear of compromising final adult height.

Sex hormones in juvenile nasopharyngeal angiofibroma tissue.

Five cases of juvenile nasopharyngeal angiofibroma were studied in terms of the presence of progesterone, estradiol, testosterone, and dihydrotestosterone in the juvenile nasopharyngeal angiofibroma tissue using the peroxidase-antiperoxidase method. Progesterone and estradiol were positive in all cases. Testosterone was positive in 2 of the 5 patients. Dihydrotestosterone was positive in 3 of the 5 patients. Hormone in the juvenile nasopharyngeal angiofibroma tissue seems to change by the activity of nasopharyngeal angiofibroma.

Deflazacort and fluoximesterone in advanced, pretreated breast cancer.

A very simple, low dose, orally administered regime (10 to 15 mg of fluoximesterone + 6 mg of deflazacort daily for periods of 1 to several months) resulting in mild-acceptable toxicity (essentially some weight gain) determined subjective improvement in 2/3 of 34 evaluable patients (out of 36 treated) and an objective measurable tumor reduction in 1/3, although most patients had been previously treated with chemotherapy and hormone treatment and proved primarily or secondarily refractory. The receptor status at the beginning of fluoximesterone+deflazacort treatment was not known, except in one negative-receptor patient, who responded to the combination after becoming resistant to tamoxifen (see photo). In some patients the condition of hormone refractoriness would suggest a no-treatment policy, but a trial with this regime is always convenient as it may improve both duration and quality of life.

Factors predicting for response, time to treatment failure, and survival in women with metastatic breast cancer treated with DAVTH: a prospective Eastern Cooperative Oncology Group study.

Six hundred twenty-four women with metastatic breast cancer were entered on Eastern Cooperative Oncology Group (ECOG) study EST 2181. Patients were treated with mitolactol, doxorubicin, vincristine (DAV), tamoxifen, and fluoxymesterone (DAVTH). Nine patients were canceled, and 114 were ineligible (half because of concomitant diseases). Among the 501 eligible patients, the overall response rate was 54% (14% complete response and 5% not assessable). The median time to treatment failure (TTF) was 9.0 months, and the median survival was 20.9 months. Multivariate models were fit on a randomly chosen half of the eligible cases and then verified on the other half. About half of the variables that were significant in the models remained significant in the verification data set. In the verification data set the variables that remained significantly associated with lower probability of response were three or more organ sites of disease and lack of nodal metastases; the variables associated with a significantly shorter TTF were liver metastases, estrogen receptor (ER)-negativity, and prior adjuvant therapy. The variables associated with significantly shorter survival were liver metastases, ER negativity, three or more organ sites of disease, and prior adjuvant chemotherapy. None of the variables in the data set had a significant influence on toxicity. The 125 patients aged over 65 years did not have worse toxicity or worse prognosis than younger patients. Ineligible patients had significantly less response but virtually identical TTF curves, survival curves, and toxicities. Therefore, patient discriminants are of paramount importance in predicting the outcome of treatment. Many of the current criteria for eligibility for entry on study may not be justified.

Adjuvant therapy of stage II breast cancer treated with CMFVP, radiation therapy and VATH following lumpectomy. A pilot trial.

A pilot study was undertaken to assess the feasibility, toxicity, and efficacy of combined radiation therapy and chemotherapy in the adjuvant treatment of node-positive. Stage II patients with breast carcinoma who had undergone lumpectomy. Therapy consisted of three phases, starting with a six-week CMFVP (cyclophosphamide, methotrexate, 5-fluorouracil, vincristine, prednisone) induction, followed by radiation therapy to the breast, and concluding with four cycles of VATH (vinblastine, Adriamycin, thiotepa, Halotesin). Twenty-seven patients were entered with an average age of 51.5 years (median 50 yrs) and a mean follow-up of 46.2 months. Twenty-three patients (85.2%) are alive and 19 (70.3%) disease free. There were no ipsilateral local recurrences. Cosmetic results were good to excellent in 26/27 patients. The doses of VATH were not compromised by the prior therapy. The regimen was found to be tolerable and is a reasonable approach in the adjuvant treatment of this particular patient population.