Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel with planned crossover to the alternate single agent in metastatic breast cancer

Seidman, Andrew D.; Brufsky, Adam; Ansari, Rafat; Hart, Lowell L.; Stein, Richard S.; Schwartzberg, Lee S.; Stewart, John; Russell, Christy; Chen, Sheng-Chi; Fein, Luis; Cruz-Vargas, Jhony A. De La; Kim, S.-B.; Cavalheiro, José Antônio Crespo; Zhao, Luping; Gill, James J.; Obasaju, Coleman K.; Orlando, Mauro; Tai, D. F.

doi:10.1093/annonc/mdq578

Cited by 30 publications

(37 citation statements)

References 25 publications

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“…The non-hematological side effects reflect the lower taxane dose, the use of gemcitabine in the FEC-DG arm and the standard docetaxel 100 mg dose in the FEC-D arm. In the FEC-DG arm, gemcitabine caused a significant elevation of SGPT and/or SGOT, which is consistent with other trials and is well described as a limiting factor for dose escalation [27,28]. An example is the Neo-tAnGo trial [29], which included neoadjuvant gemcitabine in combination with paclitaxel before or after epirubicin/cyclophosphamide treatment where additional gemcitabine also resulted in increased rates of transaminitis.…”

supporting

confidence: 78%

Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial

Schröder

Rack

Sommer

et al. 2016

Geburtshilfe Frauenheilkd

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!Introduction: This paper aims to evaluate the toxicity profile of additive gemcitabine to adjuvant taxane-based chemotherapy in breast cancer patients. Methods: Patients enrolled in this open-label randomized controlled Phase III study were treated with 3 cycles of epirubicin-fluorouracil-cyclophosphamide (FEC) chemotherapy followed by 3 cycles of docetaxel with those receiving 3 cycles of FEC followed by 3 cycles of gemcitabine-docetaxel (FEC-DG). 3690 patients were evaluated according to National Cancer Institute (NCI) toxicity criteria (CTCAE). The study medications were assessed by the occurrence of grade 3-4 adverse events, dose reductions, postponements of treatment cycles and granulocyte colony-stimulating factor (G-CSF) support. Results: No differences in neutropenia or febrile neutropenia were demonstrated. However, thrombocytopenia was significantly increased with FEC-DG treatment (2.0 vs. 0.5 %, p < 0.001), as was leukopenia (64.1 vs. 58.5 %, p < 0.001). With FEC-DG significantly more G-CSF support in cycles 4 to 6 (FEC-DG: 57.8 %, FEC-D: 36.3 %, p < 0.001) was provided. Transaminase elevation was significantly more common with FEC-DG (SGPT: 6.3 %, SGOT: 2%), whereas neuropathy (1.2 %), arthralgia (1.6 %) and bone pain (2.6 %) were more common using FEC-D. Dose reductions > 20 % (4 vs. 2.4 %) and postponement of treatment cycles (0.9 vs. 0.4 %) were significantly more frequent in the FEC-DG arm. Eight deaths occurred during treatment in the FEC-DG arm and four in the FEC-D arm. Conclusion: The addition of gemcitabine increased hematological toxicity and was associated with more dose reductions and postponements of treatment cycles.

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supporting

confidence: 78%

Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial

Schröder

Rack

Sommer

et al. 2016

Geburtshilfe Frauenheilkd

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“…The authors suggest that gemcitabine may be a better option than capecitabine in combination with docetaxel in that patient population. More recently, a highly powered phase III randomized trial of gemcitabine/docetaxel versus capecitabine/docetaxel in advanced breast cancer, with planned crossover to the alternate single agent, was published [25]. The two treatments showed similar efficacy in terms of response rate, time to progression and overall survival, and toxicity profiles were higher for the capecitabine/docetaxel arm, consistent with prior clinical experience [25].…”

Section: Discussionsupporting

confidence: 56%

“…Certainly, there are specific situations in which it is mandatory to rapidly obtain a tumor response, such as for ‘aggressive’ cancers with fast growing or symptomatic visceral metastases, and in this context, the two docetaxel-based doublets evaluated in our trial both represent a valid option in HER-2-negative breast cancer patients relapsing after an anthracycline-based adjuvant regimen. A possible suggestion may be to prefer the gemcitabine/docetaxel doublet as first option, considering that capecitabine maintains its activity also as a single agent and in heavily pretreated patients [24,25] and the higher therapeutic index of the docetaxel/gemcitabine regimen in comparison with the docetaxel/capecitabine doublet observed in our study.…”

Section: Discussionmentioning

confidence: 99%

A Multicenter Phase II Randomized Trial of Docetaxel/Gemcitabine versus Docetaxel/Capecitabine as First-Line Treatment for Advanced Breast Cancer: A Gruppo Oncologico Italia Meridionale Study

Vici¹,

Giotta²,

Lauro³

et al. 2011

Oncology

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Objective: To evaluate two docetaxel-based regimens as first-line treatment in advanced breast cancer patients. Methods: Patients were randomly assigned to docetaxel/gemcitabine (arm A: docetaxel 75 mg/m² on day 1, gemcitabine 1,000 mg/m² on days 1 and 8) or docetaxel/capecitabine (arm B: docetaxel 75 mg/m² on day 1, capecitabine 1,250 mg/m² twice daily on days 1–14); both chemotherapy regimens were repeated every 21 days. The primary objective of the study was to evaluate the response rate. Results: Seventy-two patients were enrolled (36 each in arms A and B). Responses according to intention-to-treat analysis were as follows: arm A, 41.7% [95% confidence interval (CI) 25.6–57.8]; arm B, 38.9% (95% CI 23–54.8). Median progression-free survival was 10.9 months (95% CI 8.1–13.7) in arm A and 10 months (95% CI 8.8–11.2) in arm B. Overall survival was 26 months (95% CI 22.0–30.0) in arm A and 28 months (95% CI 23.4–32.6) in arm B. Both treatments were well tolerated; myelosuppression was the dose-limiting toxicity, with grade 3–4 neutropenia in 13.8 and 19.4% of the patients in arms A and B, respectively. No relevant differences in other toxicities were observed in the two arms, except for diarrhea (13.9%) and hand-foot syndrome (11.1%), which occurred only in arm B. Conclusions: Both regimens were active and well tolerated in advanced breast cancer.

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“…The combination was associated with a relatively high incidence of toxicity, particularly hand-foot syndrome and gastrointestinal toxicities, leading to frequent dose modification or treatment interruption. More recently, the XT combination has been tested in the first-line setting, typically using a lower capecitabine dose in combination with docetaxel [4,5]. Three phase III trials compared first-line XT with alternative docetaxel-containing doublets in HER2-negative MBC [4,5,6].…”

Section: Introductionmentioning

confidence: 99%

“…More recently, the XT combination has been tested in the first-line setting, typically using a lower capecitabine dose in combination with docetaxel [4,5]. Three phase III trials compared first-line XT with alternative docetaxel-containing doublets in HER2-negative MBC [4,5,6]. In addition, the randomized, phase II CHAT trial compared XT versus docetaxel, with trastuzumab given in both arms, as first-line therapy for HER2-positive MBC [7].…”

Section: Introductionmentioning

confidence: 99%

Final Results of ERASME-4: A Randomized Trial of First-Line Docetaxel plus either Capecitabine or Epirubicin for Metastatic Breast Cancer

et al. 2011

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Objective: To assess the efficacy of capecitabine plus docetaxel (XT) versus epirubicin plus docetaxel (ET) as first-line therapy for metastatic breast cancer (MBC). Patients and Methods: Patients with no prior chemotherapy for MBC were randomized to 3-weekly cycles of either XT (capecitabine 1,000 mg/m² twice daily, days 1–14; docetaxel 75 mg/m², day 1) or ET (epirubicin 75 mg/m², day 1; docetaxel 75 mg/m², day 1). The primary endpoint was non-progression rate 6 months after randomization. The planned sample size was 106 patients based on a randomized, phase II selection design. Results: Between April 2004 and January 2007, 68 patients were randomized, giving 82% power to select the best regimen according to a 6-month non-progression rate. Slow accrual led to premature study termination. Baseline characteristics were generally well balanced between arms. The 6-month non-progression rates were 75.8% with XT versus 65.7% with ET (p = 0.36). After 42 months’ median follow-up, median progression-free survival was 12.4 versus 6.8 months, respectively (p = 0.040). The safety profiles were consistent with previous experience. Conclusion: Further larger studies are warranted to validate these results. Despite more grade 3 hand-foot syndrome, first-line XT may be a valid alternative to ET, potentially improving efficacy.

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Phase III trial of gemcitabine plus docetaxel versus capecitabine plus docetaxel with planned crossover to the alternate single agent in metastatic breast cancer

Abstract: GD and CD produced similar efficacy and toxicity profiles consistent with prior clinical experience.

Cited by 30 publications

References 25 publications

Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial

Toxicity Assessment of a Phase III Study Evaluating FEC-Doc and FEC-Doc Combined with Gemcitabine as an Adjuvant Treatment for High-Risk Early Breast Cancer: the SUCCESS-A Trial

A Multicenter Phase II Randomized Trial of Docetaxel/Gemcitabine versus Docetaxel/Capecitabine as First-Line Treatment for Advanced Breast Cancer: A Gruppo Oncologico Italia Meridionale Study

Final Results of ERASME-4: A Randomized Trial of First-Line Docetaxel plus either Capecitabine or Epirubicin for Metastatic Breast Cancer

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