Phase II Study of Docetaxel, Doxorubicin, and Cyclophosphamide as First-Line Chemotherapy for Metastatic Breast Cancer

Nabholtz, Jean‐Marc; Mackey, John R.; Smylie, Michael; Paterson, Alexander; Noel, D.; Al‐Tweigeri, Taher; Tonkin, Katia; North, Scott; Azli, N.; Riva, A.

doi:10.1200/jco.2001.19.2.314

Cited by 106 publications

(62 citation statements)

References 19 publications

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“…75,76 Similar cardiotoxicity was not seen in phase I-II studies when docetaxel was used in combination with doxorubicin, although the increased efficacy was maintained. [77][78][79][80] Based on the above studies, as well as phase III trials, 82 the NSABP B-30 study was designed to directly compare the sequential regimen of AC followed by docetaxel to the combination of doxorubicin plus docetaxel and to the triple combination of doxorubicin plus docetaxel plus cyclophosphamide. ( figure 13) This trial was initiated in 1999 and has accrued more than 4,500 of the 5,300 patients needed.…”

Section: Studies Evaluating Dose-intensificationmentioning

confidence: 99%

NSABP Breast Cancer Clinical Trials: Recent Results and Future Directions

Mamounas¹

2003

Clinical Medicine & Research

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Over the past 40 years, the National Surgical Adjuvant Breast and Bowel Project (NSABP) has conducted several large, randomized clinical trials evaluating various aspects of surgical and adjuvant therapy in patients with operable breast cancer. Results from these trials have contributed significantly in reducing the extent of surgical procedures and in improving the outcome of patients with early-stage breast cancer. Furthermore, they have helped to establish standards of care for the surgical management of invasive and non-invasive disease and for the use of adjuvant hormonal therapy and adjuvant chemotherapy for patients with negative as well as for those with positive axillary nodes. More recent trials are evaluating several new classes of promising drugs such as the aromatase inhibitors in postmenopausal women with invasive or intraductal breast cancer, the taxanes for patients with positive nodes and in the neoadjuvant setting and other targeted molecular therapies such as trastuzumab and bisphosphonates. Results from these ongoing and recently completed trials could improve outcomes and quality of life for patients with early-stage breast cancer.

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Section: Studies Evaluating Dose-intensificationmentioning

confidence: 99%

NSABP Breast Cancer Clinical Trials: Recent Results and Future Directions

Mamounas¹

2003

Clinical Medicine & Research

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“…However, there was no difference in response rates in relation to the type of taxane that was used for re-challeng (table 2). [18][19][20]. The response rate of paclitaxel monotherapy is largely dependent on dosing, infusion time and scheduling, and ranged between 22 and 62% [21,22].…”

Section: Discussionmentioning

confidence: 99%

Rechallenging taxanes in recurrent breast cancer in patients treated with (neo-) adjuvant taxane-based therapy.

Guo¹,

Loibl²,

Untch³

et al. 2011

JCO

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Keywords Docetaxel · Paclitaxel · Adjuvant · Recurrent breast cancer SummaryBackground: Docetaxel and paclitaxel are among the most active substances for the treatment of breast cancer. As both drugs are used today in adjuvant regimens, efficacy data from pivotal trials in the metastatic setting in taxanenaive populations cannot reliably be used as references. Patients and Methods:The Taxane Re-Challenge Cohort Study identified participants from 6 prospective (neo-)adjuvant taxane-based studies with recurrent disease and collected data on their subsequent treatment. Out of 381 recurrent patients, 106 (27.8%) were re-challenged with a taxane-based treatment as first-or later-line therapy for recurrent disease. Results: Taxanes were used as first-line therapy in 74 patients and showed a response rate of 48.6% (including complete responses in 27.0%). The response rate was dependent on the disease-free interval (< 1 year: 34.8%; 1-2 years: 42.9%; > 2 years: 63.3%; p = 0.04) and visceral metastasis (present: 62.5%; not present 32.4%; p = 0.01). Patients without visceral metastasis and with a disease-free interval of > 2 years achieved the longest overall survival. Hormone and HER2 receptor status were not predictive; however, triple-negative tumors responded in 50.0%. The overall response rate of later-line taxane-based treatment was 28.2%. Conclusion: Re-challenging taxanes appears to be effective and therefore represents a reasonable option in this population.

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“…Women with metastatic breast cancer are generally considered as incurable, with a median survival of about 2 years after documentation of metastases (Honig, 1996). Conventional chemotherapy regimens produce 40 to 80% objective response rates with median time to progression of less than 1 year (Clavel and Catimel, 1993;Nabholtz et al, 2001). Until now, high-dose chemotherapy (HDCT) regimens with autologous bone marrow or peripheral blood progenitor cell (PBPC) reinfusion have yielded high response rates, but demonstrated no survival improvement, in particular no obvious increase in the rate of long term survivors in currently available phase III trials (Stadtmauer et al, 2000;Antman, 2001).…”

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confidence: 99%

A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients

et al. 2002

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This pilot phase I/II study intended to determine the maximum tolerated dose of cyclophosphamide and thiotepa administered on four consecutive courses with peripheral blood progenitor cell and granulocyte-colony stimulating factor support, as firstline therapy for hormone-refractory metastatic breast cancer patients. Twenty-eight patients were entered in the study. After two courses of epirubicin (120 mg m 72 ) and cyclophosphamide (2 g m 72 ) followed by granulocyte-colony stimulating factor injection and leukaphereses, patients received four cycles of cyclophosphamide and thiotepa. Each cycle was followed by peripheral blood progenitor cell and granulocyte-colony stimulating factor supports, then repeated every 28 to 35 days. Six escalating dose levels of cyclophosphamide and thiotepa were planned, beginning at cyclophosphamide 1.5 g m 72 and thiotepa 200 mg m 72 . At least three patients were enrolled for each dose level. Eighteen patients completed the study. The maximum tolerated dose was 3000 mg m 72 cyclophosphamide and 400 mg m 72 thiotepa per course. Haematological toxicity was manageable on an outpatient basis and did not increase significantly with dose escalation. Dose-limiting toxicity was chemotherapy-induced immuno-suppression, which resulted in one toxic death and two life-threatening infections. Median times to treatment failure and survival were 11 and 26 months, respectively. Three patients were alive, free of disease 30 months after completion of the study. Such therapy allows for high-dose intensity and high cumulative doses on a short period of time with manageable toxicity.

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Phase II Study of Docetaxel, Doxorubicin, and Cyclophosphamide as First-Line Chemotherapy for Metastatic Breast Cancer

Abstract: TAC is an active and manageable regimen that has been chosen as the basis of five randomized phase III trials, including two pivotal studies comparing TAC to fluorouracil plus doxorubicin and cyclophosphamide in the metastatic and adjuvant treatment of breast cancer.

Cited by 106 publications

References 19 publications

NSABP Breast Cancer Clinical Trials: Recent Results and Future Directions

NSABP Breast Cancer Clinical Trials: Recent Results and Future Directions

Rechallenging taxanes in recurrent breast cancer in patients treated with (neo-) adjuvant taxane-based therapy.

A phase I/II study of 4 monthly courses of high-dose cyclophosphamide and thiotepa for metastatic breast cancer patients

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