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1. Doxorubicin and cisplatin chemotherapy in high-grade spindle cell sarcomas of the bone, other than osteosarcoma or malignant fibrous histiocytoma: a European Osteosarcoma Intergroup Study

Author

UCL, Nooij, MA, Whelan, Jeremy S., Bramwell, VHC, Taminiau, AT, Cannon, S, Hogendoorn, PCW, Pringle, J, Uscinska, Barbara M., Weeden, S, Kirkpatrick, A, von Glabbeke, M, Craft, AW, UCL, Nooij, MA, Whelan, Jeremy S., Bramwell, VHC, Taminiau, AT, Cannon, S, Hogendoorn, PCW, Pringle, J, Uscinska, Barbara M., Weeden, S, Kirkpatrick, A, von Glabbeke, M, and Craft, AW

Abstract

There are limited data that define the role of chemotherapy in the treatment of high-grade spindle cell sarcomas of bone, other than osteosarcoma or malignant fibrous histiocytoma (MFH-B). This prospective study evaluates the effect of doxorubicin and cisplatin on these tumours. Thirty-seven patients, age less than or equal to65 years, with spindle cell sarcoma of bone, except osteosarcoma, or MFH-B, were included. Chemotherapy consisted of doxorubicin and cisplatin every 3 weeks for six cycles. Resection was performed after three cycles. In 15 patients with metastases, response assessment showed three complete responses (CR), four stable disease (SD), five progression; three were not evaluable. Median time to progression was 30 months (95% Confidence Interval (CI), 851 months) for the operable non-metastatic patients; median survival 41 months (95% CI, 16-82 months). Median time to progression in the metastatic group was 10 months (95% CI, 0-18 months) and median survival was 14 months (95% CI, 4-45 months). This study suggests a limited role for doxorubicin and cisplatin in metastatic high-grade spindle cell sarcoma of bone, other than osteosarcoma or MFH-B cases. (C) 2004 Elsevier Ltd. All rights reserved.

Published
2005

2. Neoadjuvant chemotherapy with doxorubicin and cisplatin in malignant fibrous histiocytoma of bone: A European osteosarcoma intergroup study

Author

UCL, Bramwell, VHC, Steward, WP, Nooij, M., Whelan, Jeremy S., Craft, AW, Grimer, RJ, Taminau, AHM, Cannon, SR, Malcolm, AJ, Hogendoorn, PCW, Uscinska, Barbara M., Kirkpatrick, AL, Machin, D, Van Glabbeke, MM, UCL, Bramwell, VHC, Steward, WP, Nooij, M., Whelan, Jeremy S., Craft, AW, Grimer, RJ, Taminau, AHM, Cannon, SR, Malcolm, AJ, Hogendoorn, PCW, Uscinska, Barbara M., Kirkpatrick, AL, Machin, D, and Van Glabbeke, MM

Abstract

Purpose: Studies involving small ease series have suggested that malignant fibrous histiocytoma of bone (MFH-B) is a chemosensitive tumor and that chemotherapy may improve survival, In this study, we evaluated clinical and pathologic response rates and survival in a series of patients treated with a consistent chemotherapy regimen of doxorubicin and cisplatin (DOX/DDP), Patients and Methods: Study patients were required to have biopsy-proven MFH-B, no previous chemotherapy, and primary or metastatic measurable disease and to be less than or equal to 65 years of age, Treatment consisted of doxorubicin 25 mg/m(2)/d days 1 through 3 and cisplatin 100 mg/m(2) by 4-hour intravenous infusion every 3 weeks for six cycles. In patients with operable primary tumors, chemotherapy was planned to start within 42 days of biopsy, with definitive surgery performed after three cycles. Results: Forty-one patients herd operable nonmetastatic limb sarcomas, and 23 (56%) completed six chemotherapy cycles. Limb salvage was possible in 33 patients (80%), and 16 (42%) of 38 assessable specimens showed a good pathologic response (greater than or equal to 90% necrosis), Median time to progression was 56 months, and the 5-year progression-free survival rate was 56% (95% confidence interval [CI], 40% to 72%). Median survival time war 63 months, and the 5-year survival rate was 59% (95% CI, 41% to 77%). Patients with a good pathologic response had longer survival times and times to progression than did those with a poor response. Also treated were two patients with locally recurrent and nine with metastatic disease, and these patients had a median survival time of 17.5 months. Conclusion: Our study suggests that adjuvant or neoadjuvant chemotherapy with DOX/DDP is beneficial in MFH-B, Good pathologic response rates and survivors are quite comparable with those far osteosarcoma, a related bone tumor for which adjuvant or neoadjuvant chemotherapy is an accepted practice. (C) 1999 by American Soci

Published
1999

5. Impact of baseline BMI and weight change in CCTG adjuvant breast cancer trials.

Author

Yerushalmi R, Dong B, Chapman JW, Goss PE, Pollak MN, Burnell MJ, Levine MN, Bramwell VHC, Pritchard KI, Whelan TJ, Ingle JN, Shepherd LE, Parulekar WR, Han L, Ding K, and Gelmon KA

Subjects
Antineoplastic Agents adverse effects, Breast Neoplasms mortality, Breast Neoplasms pathology, Chemotherapy, Adjuvant, Disease Progression, Disease-Free Survival, Female, Humans, Middle Aged, Perimenopause, Postmenopause, Premenopause, Randomized Controlled Trials as Topic, Risk Factors, Time Factors, Treatment Outcome, Antineoplastic Agents administration & dosage, Body Mass Index, Breast Neoplasms drug therapy, Neoadjuvant Therapy, Weight Gain
Abstract

Background: We hypothesized that increased baseline BMI and BMI change would negatively impact clinical outcomes with adjuvant breast cancer systemic therapy., Methods: Data from chemotherapy trials MA.5 and MA.21; endocrine therapy MA.12, MA.14 and MA.27; and trastuzumab HERA/MA.24 were analyzed. The primary objective was to examine the effect of BMI change on breast cancer-free interval (BCFI) landmarked at 5 years; secondary objectives included BMI changes at 1 and 3 years; BMI changes on disease-specific survival (DSS) and overall survival (OS); and effects of baseline BMI. Stratified analyses included trial therapy and composite trial stratification factors., Results: In pre-/peri-/early post-menopausal chemotherapy trials (N = 2793), baseline BMI did not impact any endpoint and increased BMI from baseline did not significantly affect BCFI (P = 0.85) after 5 years although it was associated with worse BCFI (P = 0.03) and DSS (P = 0.07) after 1 year. BMI increase by 3 and 5 years was associated with better DSS (P = 0.01; 0.01) and OS (P = 0.003; 0.05). In pre-menopausal endocrine therapy trial MA.12 (N = 672), patients with higher baseline BMI had worse BCFI (P = 0.02) after 1 year, worse DSS (P = 0.05; 0.004) after 1 and 5 years and worse OS (P = 0.01) after 5 years. Increased BMI did not impact BCFI (P = 0.90) after 5 years, although it was associated with worse BCFI (P = 0.01) after 1 year. In post-menopausal endocrine therapy trials MA.14 and MA.27 (N = 8236), baseline BMI did not significantly impact outcome for any endpoint. BMI change did not impact BCFI or DSS after 1 or 3 years, although a mean increased BMI of 0.3 was associated with better OS (P = 0.02) after 1 year. With the administration of trastuzumab (N = 1395) baseline BMI and BMI change did not significantly impact outcomes., Conclusions: Higher baseline BMI and BMI increases negatively affected outcomes only in pre-/peri-/early post-menopausal trial patients. Otherwise, BMI increases similar to those expected in healthy women either did not impact outcome or were associated with better outcomes., Clinical Trials Numbers: CAN-NCIC-MA5; National Cancer Institute (NCI)-V90-0027; MA.12-NCT00002542; MA.14-NCT00002864; MA.21-NCT00014222; HERA, NCT00045032;CAN-NCIC-MA24; MA-27-NCT00066573., (© The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Published
2017
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6. A randomized placebo-controlled study of tamoxifen after adjuvant chemotherapy in premenopausal women with early breast cancer (National Cancer Institute of Canada--Clinical Trials Group Trial, MA.12).

Author

Bramwell VHC, Pritchard KI, Tu D, Tonkin K, Vachhrajani H, Vandenberg TA, Robert J, Arnold A, O'Reilly SE, Graham B, and Shepherd L

Subjects
Academies and Institutes, Adult, Antineoplastic Agents administration & dosage, Breast Neoplasms mortality, Breast Neoplasms pathology, Breast Neoplasms surgery, Canada, Chemotherapy, Adjuvant, Disease Progression, Drug Administration Schedule, Female, Humans, Lymph Node Excision, Mastectomy methods, Middle Aged, Placebos, Survival Analysis, Time Factors, Breast Neoplasms drug therapy, Premenopause drug effects, Tamoxifen administration & dosage
Abstract

Background: In the early 1990s, the role of adjuvant tamoxifen in premenopausal women with early breast cancer (EBC) was not established. Similarly, optimum timing relative to adjuvant chemotherapy and efficacy of tamoxifen in hormone receptor-negative tumors were unclear., Patients and Methods: Premenopausal women with EBC, any hormone receptor status, after surgery received standard adjuvant chemotherapy [doxorubicin (adriamycin)/cyclophosphamide, cyclophosphamide/methotrexate/5-fluorouracil, or cyclophosphamide/epirubicin/5-fluorouracil] followed by randomization to tamoxifen or placebo for 5 years. Outcomes were overall survival (OS), disease-free survival (DFS), toxicity, and compliance with therapy., Results: Median follow-up for 672 women was 9.7 years. Multivariate analysis showed improved DFS [78.2% versus 71.3% at 5 years; hazard ratio (HR) 0.77; P = 0.056] and a trend for improved OS (86.6% versus 82.1% at 5 years; HR 0.78; P = 0.12). There was no evidence of greater benefit for the receptor-positive subgroup. Compliance with treatment was suboptimal in both arms, with 103 (31%) women on tamoxifen and 70 (21%) on placebo-stopping therapy early because of toxicity, refusal, or other choices., Conclusions: Adjuvant tamoxifen, given after chemotherapy to premenopausal women with EBC, improved 5-year DFS. Poor compliance may have reduced treatment efficacy.

Published
2010
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