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Title: Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study

Abstract

Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion:more » adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.« less

Authors:
; ; ;
Publication Date:
Research Org.:
Netherlands Cancer Institute, Amsterdam
OSTI Identifier:
6041661
Resource Type:
Journal Article
Resource Relation:
Journal Name: Int. J. Radiat. Oncol., Biol. Phys.; (United States); Journal Volume: 10
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; CHEMOTHERAPY; EVALUATION; RADIOTHERAPY; DOXORUBICIN; ENDOXAN; FLUOROURACILS; LYMPH NODES; MAMMARY GLANDS; MENOPAUSE; METHOTREXATE; ONCOVIN; PATIENTS; ALKALOIDS; ALKYLATING AGENTS; ANTI-INFECTIVE AGENTS; ANTIBIOTICS; ANTIMETABOLITES; ANTIMITOTIC DRUGS; ANTINEOPLASTIC DRUGS; AZINES; BODY; DRUGS; GLANDS; HETEROCYCLIC COMPOUNDS; HYDROXY COMPOUNDS; IMMUNOSUPPRESSIVE DRUGS; LYMPHATIC SYSTEM; MEDICINE; NUCLEAR MEDICINE; ORGANIC COMPOUNDS; ORGANIC FLUORINE COMPOUNDS; ORGANIC HALOGEN COMPOUNDS; ORGANIC NITROGEN COMPOUNDS; ORGANS; PYRIMIDINES; RADIOLOGY; THERAPY; URACILS; 550603* - Medicine- External Radiation in Therapy- (1980-)

Citation Formats

Schaake-Koning, C., van der Linden, E.H., Hart, G., and Engelsman, E.. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study. United States: N. p., 1985. Web. doi:10.1016/0360-3016(85)90028-8.
Schaake-Koning, C., van der Linden, E.H., Hart, G., & Engelsman, E.. Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study. United States. doi:10.1016/0360-3016(85)90028-8.
Schaake-Koning, C., van der Linden, E.H., Hart, G., and Engelsman, E.. Tue . "Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study". United States. doi:10.1016/0360-3016(85)90028-8.
@article{osti_6041661,
title = {Adjuvant chemo- and hormonal therapy in locally advanced breast cancer: a randomized clinical study},
author = {Schaake-Koning, C. and van der Linden, E.H. and Hart, G. and Engelsman, E.},
abstractNote = {Between 1977 and 1980, 118 breast cancer patients with locally advanced disease, T3B-4, any N, M0 or T1-3, tumor positive axillary apex biopsy, were randomized to one of three arms: I: radiotherapy (RT) to the breast and adjacent lymph node areas; II: RT followed by 12 cycles of cyclophosphamide, methotrexate, 5 fluorouracil (CMF) and tamoxifen during the chemotherapy period; III: 2 cycles of adriamycin and vincristine (AV), alternated with 2 cycles of CMF, then RT, followed by another 4 cycles of AV, alternated with 4 CMF; tamoxifen during the entire treatment period. The median follow-up period was 5 1/2 years. The adjuvant chemo- and hormonal therapy did not improve the overall survival; the 5-year survival was 37% for all three treatment arms. There was no statistically significant difference in RFS between the three modalities, nor when arm I was compared to arm II and III together. LR was not statistically different over the three treatment arms. In 18 of the 24 patients with LR, distant metastases appeared within a few months from the local recurrence. The menopausal status did not influence the treatment results. Dose reduction in more than 4 cycles of chemotherapy was accompanied by better results. In conclusion: adjuvant chemo- and hormonal therapy did not improve RFS and overall survival. These findings do not support the routine use of adjuvant chemo- and endocrine therapy for inoperable breast cancer.},
doi = {10.1016/0360-3016(85)90028-8},
journal = {Int. J. Radiat. Oncol., Biol. Phys.; (United States)},
number = ,
volume = 10,
place = {United States},
year = {Tue Oct 01 00:00:00 EDT 1985},
month = {Tue Oct 01 00:00:00 EDT 1985}
}
  • Between June 1977 and April 1983 the Radiation Therapy Oncology Group (RTOG) sponsored a Phase III randomized trial investigating the use of fast neutron radiotherapy for patients with locally advanced (Stages C and D1) adenocarcinoma of the prostate gland. Patients were randomized to receive either conventional photon radiation or fast neutron radiation used in a mixed-beam (neutron/photon) treatment schedule. A total of 91 analyzable patients were entered into the study, and the two patient groups were balanced with respect to the major prognostic variables. Actuarial curves are presented for local/regional control and "overall" survival. Ten-year results for clinically assessed localmore » control are 70% for the mixed-beam group versus 58% for the photon group (p = 0.03) and for survival are 46% for the mixed-beam group versus 29% for the photon group (p = 0.04). This study suggests that a regional method of treatment can influence both local tumor control and survival in patients with locally advanced adenocarcinoma of the prostate gland.« less
  • Background and Purpose: Brachytherapy in the treatment of locally advanced cervical cancer has changed substantially because of the introduction of combined intracavitary/interstitial applicators and an adaptive target concept, which is the focus of the prospective, multi-institutional EMBRACE study ( (www.embracestudy.dk)) on image-guided adaptive brachytherapy (IGABT). So far, little has been reported about the development of early to late vaginal morbidity in the frame of IGABT. Therefore, the aim of the present EMBRACE analysis was to evaluate the manifestation pattern of vaginal morbidity during the first 2 years of follow-up. Methods and Materials: In total, 588 patients with a median follow-up timemore » of 15 months and information on vaginal morbidity were included. Morbidity was prospectively assessed at baseline, every 3 months during the first year, and every 6 months in the second year according to the Common Terminology Criteria for Adverse Events, version 3, regarding vaginal stenosis, dryness, mucositis, bleeding, fistula, and other symptoms. Crude incidence rates, actuarial probabilities, and prevalence rates were analyzed. Results: At 2 years, the actuarial probability of severe vaginal morbidity (grade ≥3) was 3.6%. However, mild and moderate vaginal symptoms were still pronounced (grade ≥1, 89%; grade ≥2, 29%), of which the majority developed within 6 months. Stenosis was most frequently observed, followed by vaginal dryness. Vaginal bleeding and mucositis were mainly mild and infrequently reported. Conclusion: Severe vaginal morbidity within the first 2 years after definitive radiation (chemo)therapy including IGABT with intracavitary/interstitial techniques for locally advanced cervical cancer is limited and is significantly less than has been reported from earlier studies. Thus, the new adaptive target concept seems to be a safe treatment with regard to the vagina being an organ at risk. However, mild to moderate vaginal morbidity is still pronounced with currently applied IGABT, and it needs further attention.« less
  • Purpose: To report secondary efficacy endpoints of Radiation Therapy Oncology Group protocol 0247, primary endpoint analysis of which demonstrated that preoperative radiation therapy (RT) with capecitabine plus oxaliplatin achieved a pathologic complete remission prespecified threshold (21%) to merit further study, whereas RT with capecitabine plus irinotecan did not (10%). Methods and Materials: A randomized, phase 2 trial evaluated preoperative RT (50.4 Gy in 1.8-Gy fractions) with 2 concurrent chemotherapy regimens: (1) capecitabine (1200 mg/m{sup 2}/d Monday-Friday) plus irinotecan (50 mg/m{sup 2}/wk × 4); and (2) capecitabine (1650 mg/m{sup 2}/d Monday-Friday) plus oxaliplatin (50 mg/m{sup 2}/wk × 5) for clinical T3 or T4 rectal cancer. Surgery was performed 4 tomore » 8 weeks after chemoradiation, then 4 to 6 weeks later, adjuvant chemotherapy (oxaliplatin 85 mg/m{sup 2}; leucovorin 400 mg/m{sup 2}; 5-fluorouracil 400 mg/m{sup 2}; 5-fluorouracil 2400 mg/m{sup 2}) every 2 weeks × 9. Disease-free survival (DFS) and overall survival (OS) were estimated univariately by the Kaplan-Meier method. Local–regional failure (LRF), distant failure (DF), and second primary failure (SP) were estimated by the cumulative incidence method. No statistical comparisons were made between arms because each was evaluated individually. Results: A total of 104 patients (median age, 57 years) were treated; characteristics were similar for both arms. Median follow-up for RT with capecitabine/irinotecan arm was 3.77 years and for RT with capecitabine/oxaliplatin arm was 3.97 years. Four-year DFS, OS, LRF, DF, and SP estimates for capecitabine/irinotecan arm were 68%, 85%, 16%, 24%, and 2%, respectively. The 4-year DFS, OS, LRF, DF, and SP failure estimates for capecitabine/oxaliplatin arm were 62%, 75%, 18%, 30%, and 6%, respectively. Conclusions: Efficacy results for both arms are similar to other reported studies but suggest that pathologic complete remission is an unsuitable surrogate for traditional survival metrics of clinical outcome. Although it remains uncertain whether the addition of a second cytotoxic agent enhances the effectiveness of fluorouracil plus RT, these results suggest that further study of irinotecan may be warranted.« less
  • Purpose: To evaluate the toxicity and clinical outcome in patients with locally advanced cervical cancer (LACC) treated with whole pelvic conventional radiation therapy (WP-CRT) versus intensity modulated radiation therapy (WP-IMRT). Methods and Materials: Between January 2010 and January 2012, 44 patients with International Federation of Gynecology and Obstetrics (FIGO 2009) stage IIB-IIIB squamous cell carcinoma of the cervix were randomized to receive 50.4 Gy in 28 fractions delivered via either WP-CRT or WP-IMRT with concurrent weekly cisplatin 40 mg/m{sup 2}. Acute toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 3.0, and late toxicity was gradedmore » according to the Radiation Therapy Oncology Group system. The primary and secondary endpoints were acute gastrointestinal toxicity and disease-free survival, respectively. Results: Of 44 patients, 22 patients received WP-CRT and 22 received WP-IMRT. In the WP-CRT arm, 13 patients had stage IIB disease and 9 had stage IIIB disease; in the IMRT arm, 12 patients had stage IIB disease and 10 had stage IIIB disease. The median follow-up time in the WP-CRT arm was 21.7 months (range, 10.7-37.4 months), and in the WP-IMRT arm it was 21.6 months (range, 7.7-34.4 months). At 27 months, disease-free survival was 79.4% in the WP-CRT group versus 60% in the WP-IMRT group (P=.651), and overall survival was 76% in the WP-CRT group versus 85.7% in the WP-IMRT group (P=.645). Patients in the WP-IMRT arm experienced significantly fewer grade ≥2 acute gastrointestinal toxicities (31.8% vs 63.6%, P=.034) and grade ≥3 gastrointestinal toxicities (4.5% vs 27.3%, P=.047) than did patients receiving WP-CRT and had less chronic gastrointestinal toxicity (13.6% vs 50%, P=.011). Conclusion: WP-IMRT is associated with significantly less toxicity compared with WP-CRT and has a comparable clinical outcome. Further studies with larger sample sizes and longer follow-up times are warranted to justify its use in routine clinical practice.« less
  • Purpose: To evaluate the rate of pathologic complete response (pCR) and the toxicity of two neoadjuvant chemoradiotherapy (chemoRT) regimens for Stage T3-T4 rectal cancer in a randomized Phase II study. Methods and Materials: Patients with Stage T3 or T4 rectal cancer of <12 cm from the anal verge were randomized to preoperative RT (50.4 Gy in 1.8-Gy fractions) with concurrent capecitabine (1,200 mg/m{sup 2}/d Mondays through Friday) and irinotecan (50 mg/m{sup 2} weekly in four doses) (Arm 1) or concurrent capecitabine (1,650 mg/m{sup 2}/d Monday through Friday) and oxaliplatin (50 mg/m{sup 2} weekly in five doses) (Arm 2). Surgery wasmore » performed 4-8 weeks after chemoRT, and adjuvant chemotherapy 4-6 weeks after surgery. The primary endpoint was the pCR rate, requiring 48 evaluable patients per arm. Results: A total of 146 patients were enrolled. The protocol chemotherapy was modified because of excessive gastrointestinal toxicity after treatment of 35 patients; 96 were assessed for the primary endpoint-the final regimen described above. The patient characteristics were similar for both arms. After chemoRT, the rate of tumor downstaging was 52% and 60% and the rate of nodal downstaging (excluding N0 patients) was 46% and 40%, for Arms 1 and 2, respectively. The pCR rate for Arm 1 was 10% and for Arm 2 was 21%. For Arm 1 and 2, the preoperative chemoRT rate of Grade 3-4 hematologic toxicity was 9% and 4% and the rate of Grade 3-4 nonhematologic toxicity was 26% and 27%, respectively. Conclusions: Preoperative chemoRT with capecitabine plus oxaliplatin for distal rectal cancer has significant clinical activity (10 of 48 pCRs) and acceptable toxicity. This regimen is currently being evaluated in a Phase III randomized trial (National Surgical Adjuvant Breast and Bowel Project R04).« less