High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer.

Peters, William P.; Ross, Maureen; Vredenburgh, J. J.; Meisenberg, Barry; Marks, Lawrence B.; Winer, Eric P.; Kurtzberg, Joanne; Bast, Robert C.; Jones, Roy B.; Shpall, Elizabeth J.

doi:10.1200/jco.1993.11.6.1132

Cited by 469 publications

(191 citation statements)

References 17 publications

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“…We believe that the first category, the STAMP-I regimen, is too toxic for routine use. The two studies (Peters et al, 1993;Nikcevich et al, 2002) that employed this carmustine-based combination reported high toxic death rates due to organ toxicity, mainly interstitial pneumonitis. Even very experienced centres that optimally exploit corticosteroids at the earliest sign of pulmonary symptoms report a 5% toxic death rate (Antman et al, 1992).…”

Section: Discussionmentioning

confidence: 99%

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

et al. 2003

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High-dose chemotherapy (HD-CT) has a role in the potentially curative treatment of several tumours. The relative efficacies of the different regimens have not been studied in comparative trials, but it is clear that toxicities differ significantly between them. We analysed the immediate and long-term toxicity in the first 100 consecutive patients treated with the CTC regimen (cyclophosphamide 6000 mg m À2 , carboplatin 1600 mg m À2 (or 20 mg ml À1 min under the curve (AUC)) both as daily 1 h infusion, thiotepa 480 mg m À2 as twice daily 30 min infusion, all divided over 4 consecutive days) followed by peripheral blood progenitor cell reinfusion (PBPC-Tx). Most patients had high-risk (n ¼ 86) or metastatic (n ¼ 4) breast cancer, or a germ cell tumour (n ¼ 8). Two patients (with a medulloblastoma and an aesthesioneuroblastoma, respectively) received CTC as off-protocol salvage regimen. The main toxicity was bone marrow suppression. Most patients had PBPC-Tx with granulocyte colony-stimulating factor (G-CSF), and the median time to neutrophil count 500 Â 10 6 l À1 and platelet count 420 Â 10 9 l À1 without transfusion independence was 10 (range 8 -25) and 13 (8 -60) days, respectively. The toxic death rate was 1%. Other frequent toxicities were neutropenic fever requiring antibiotics (n ¼ 65), central catheter-related infection (n ¼ 12) or a bleeding episode (n ¼ 48), mostly epistaxis (n ¼ 26). Reversible cardiac toxicity was seen in six patients and pulmonary events occurred in seven patients (infection (n ¼ 6), embolism (n ¼ 1)). Grade 3 -4 gastrointestinal toxicity was frequent: nausea and vomiting 55%, diarrhoea 28% and mild liver toxicity (transaminase elevations) 9%. One patient pretreated with cisplatin had a kidney transplantation 8 years after HD-CT. Late complications included reversible radiation pneumonitis (n ¼ 12) and chronic heart failure (n ¼ 2). We found five second solid malignancies and two myelodysplasias. In conclusion, the CTC regimen is associated with a moderate, mainly reversible, toxicity. Future studies need to compare the efficacy and toxicity of the different HD-CT regimens.

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Section: Discussionmentioning

confidence: 99%

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

et al. 2003

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“…At Duke University, in a phase II study Peters et al 22 reduced duration of aplasia and hospitalization. 35 However, much of the therapy-related mortality observed is due to used high-dose cyclophosphamide, cisplatinum and carmustine with autologous stem cell support as consolidation the organ toxicity due to the conditioning regimen and is independent of the source of hematopoietic support.…”

Section: Treatment Programmentioning

confidence: 99%

High-dose chemotherapy with autologous bone marrow support as consolidation after standard-dose adjuvant therapy in primary breast cancer patients with seven or more involved axillary lymph nodes

Lalisang

Hupperets²,

Haaft³

et al. 1998

Bone Marrow Transplant

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Summary:follow-up data from the CMF Milan experience suggest that even at that time no plateau has been reached. 7 Several studies and retrospective analyses suggest a sigDespite adjuvant chemotherapy the prognosis of patients with breast cancer and a high number of nificant dose-response relationship in metastatic and primary breast cancer. [8][9][10][11] Attempts to further improve these involved axillary lymph nodes is very poor. The aim of the present study was to evaluate the efficacy of highresults by increasing the dose of chemotherapy have met only limited success, mainly due to profound myelodose chemotherapy with autologous bone marrow support in patients with seven or more involved axillary suppression. Autologous bone marrow support (ABMS) offers an opportunity to overcome this problem, but lymph nodes. Nineteen patients underwent four courses of standard adjuvant chemotherapy, followed by highwhether this will lead to better results remains to be determined. dose busulphan/cyclophosphamide chemotherapy with autologous bone marrow support. The median age was High-dose cyclophosphamide has been shown to induce responses in a variety of relapsed or refractory malig-41.4 years and the median number of involved lymph nodes 11. Mucositis WHO grade у3 was observed in nancies and has been part of double alkylator therapy with autologous bone marrow support in advanced breast can-15 patients and 18 patients suffered febrile neutropenia. Transplant-related mortality was encountered in two cer. [12][13][14] Alkylating agents have shown a steep doseresponse relationship in vitro and, when combined, act patients, due to hepatic veno-occlusive disease and sepsis complicated by multi-organ failure, respectively.synergistically to produce response rates higher than those produced by single agents alone. 15,16 After a median follow-up period of 1490 days (range 582-2024 days) from diagnosis, nine patients haveThe preparative regimen busulphan and cyclophosphamide (BuCy) was introduced by Santos and colleagues 17 for relapsed and the overall event-free survival (EFS) is 42% (95% CI 19-65%). The median EFS is 487 days.the treatment of acute non-lymphoblastic leukaemia. This regimen was altered to decrease the toxicity of cyclophosHigh-dose treatment with BuCy2 in high-risk breast cancer patients is a toxic regimen and does not seem to phamide (BuCy2) by Tutschka and coworkers 18 without apparent loss of efficacy. Experience with BuCy2 showed improve disease-free survival. Keywords: adjuvant; bone marrow transplantation; a relatively low treatment-related morbidity, making this bi-alkylator preparative regimen potentially attractive for breast neoplasms drug therapy; busulphan; cyclophosphamide the treatment of solid tumors. 19 In 1991, we started a phase II study to address the question of whether adjuvant chemotherapy followed by highdose consolidation with busulphan and cyclophosphamide Adjuvant chemotherapy has demonstrated a modest, but supported by bone marrow transplantation will improve the consistent improveme...

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“…Breast cancer patients with four or more positive axillary lymph nodes have historically had a poor prognosis (Jatoi et al, 1999), even with conventional adjuvant chemotherapy (EBCTCG, 2005). A series of uncontrolled studies of high-dose chemotherapy in the 1990s, mainly using an induction/intensification strategy, in which patients received conventional chemotherapy followed by highdose chemotherapy as a late intensification regimen, produced results that showed a substantial benefit for high-dose regimens (Antman et al, 1992;Peters et al, 1993). High-dose therapy soon became a widely used treatment option for women with bad-risk breast cancer, even without supporting evidence from randomised controlled trials.…”

mentioning

confidence: 99%

Quality of life and sexual function after high-dose or conventional chemotherapy for high-risk breast cancer

Malinovszky

Gould²,

Foster

et al. 2006

Br J Cancer

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Three hundred and ninety women participated in the quality of life (QL) study of ACCOG1, a high-dose vs conventional adjuvant chemotherapy breast cancer trial, for patients with a high risk of relapse. Patients completed the European Organisation for Research and Treatment of Cancer QLQ-C30, questions on menopausal symptoms and the Sexual Activity Questionnaire. Pretreatment, 6,12, 24, 36, 48 and 60-month assessments were conducted. For the high dose group the median decrease in global QL at 6 months was significantly greater than in the conventional group. At 12 months, however, the median change had returned to 0 for both groups. Social functioning was also significantly lower in the high-dose group at 6 months, again returning to prebaseline levels for both groups after 12 months. The most persistent changes appear to be in the effect of treatment in both arms on sexual outcomes, reflected in problems with discomfort and pleasure. Both high-dose and conventional chemotherapy showed persisting negative effects on sexual health. This has not been previously reported as a long-term complication of high-dose chemotherapy. However, it did not have longterm affects on sexual habit, which appeared to return to pretreatment frequency and similar to that of conventional chemotherapy by about 12 months from treatment. Breast cancer patients with four or more positive axillary lymph nodes have historically had a poor prognosis (Jatoi et al, 1999), even with conventional adjuvant chemotherapy (EBCTCG, 2005). A series of uncontrolled studies of high-dose chemotherapy in the 1990s, mainly using an induction/intensification strategy, in which patients received conventional chemotherapy followed by highdose chemotherapy as a late intensification regimen, produced results that showed a substantial benefit for high-dose regimens (Antman et al, 1992;Peters et al, 1993). High-dose therapy soon became a widely used treatment option for women with bad-risk breast cancer, even without supporting evidence from randomised controlled trials.The Anglo Celtic 1 trial was set up to examine the potential benefit, if any, of employing high-dose chemotherapy in the treatment of early stage bad-risk breast cancer based on the involvement of the axillary nodes at diagnosis. One of the prospective substudies within the Anglo-Celtic 1 trial was to examine the impact of late intensification high-dose chemotherapy on QL. The purpose of this report is to review the detailed analysis of patient QL. Ethical approval for all parts of the study was given from the MREC for Scotland. PATIENTS AND METHODSBetween February 1995 and June 1999, 605 patients with newly diagnosed breast cancer with four or more positive lymph nodes were randomly assigned to either conventional (n ¼ 298) or highdose treatment (n ¼ 307). Both treatment arms initially received four cycles of doxorubicin 75 mg m À2 . Patients in the conventional arm then received eight further cycles of CMF (cyclophosphamide (600 mg m À2 ), methotrexate (50 mg m À2 ) and 5-fluorouracil (600 mg m...

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High-dose chemotherapy and autologous bone marrow support as consolidation after standard-dose adjuvant therapy for high-risk primary breast cancer.

Cited by 469 publications

References 17 publications

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience

High-dose chemotherapy with autologous bone marrow support as consolidation after standard-dose adjuvant therapy in primary breast cancer patients with seven or more involved axillary lymph nodes

Quality of life and sexual function after high-dose or conventional chemotherapy for high-risk breast cancer

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