Feasibility Study of Docetaxel with Cyclophosphamide as Adjuvant Chemotherapy for Japanese Breast Cancer Patients

Abstract

Objective: The 7-year follow-up of the US oncology 9735 trial demonstrated the superiority of TC [docetaxel (DTX)/cyclophosphamide (CPA)] to doxorubicin/CPA therapy. To introduce TC therapy in Japan, the verification of the safety and tolerability is essential. We performed a collaborative prospective safety study with Okayama University to introduce TC therapy. Methods: The subjects were 53 patients aged from 33 to 67 years at intermediate risk based on the St Gallen risk classification who underwent radical surgery for primary breast cancer between August 2007 and December 2008. As post-operative adjuvant chemotherapy, four cycles of TC (DTX 75 mg/m 2 þ CPA 600 mg/m 2 ) were administered at 3-week intervals. Adverse events were evaluated based on National Cancer Institute-Common Terminology Criteria for Adverse Events ver. 3.0. The safety and completion rate were evaluated as the primary and secondary endpoints, respectively. Results: Regarding hematological toxicity, Grade (G) 4 neutropenia occurred in 71.7% and G3 in 26.4%. G3 -4 leukopenia developed in 32.1% and 56.6%, respectively, G4 anemia in 1.9% and G1 -2 anemia in 26.4%. Regarding non-hematological toxicity, systemic malaise, skin eruption, edema, myalgia, arthralgia and nausea were noted in most patients. The completion rate was 94.3%, dose reduction was necessary in 7.5% and granulocyte colonystimulating factor (G-CSF) support was required in 17.0%. On comparison between patients aged 65 years or older and younger than 65 years, the completion rate, dose reduction and incidence of febrile neutropenia (FN) were higher in the elderly patients. G-CSF support was more often needed in this subgroup. Conclusions: TC therapy is tolerable for Japanese patients, but attention should be paid to the development of FN and neutropenia. The completion rate was lower in the elderly patients, showing that tolerability was not necessarily favorable.

Feasibility Study of Docetaxel and Cyclophosphamide Six- Cycle Therapy as Adjuvant Chemotherapy for Japanese Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer Patients

“…Neither prophylactic antibiotics nor GCSF were routinely used in this trial. The incidence of FN and the completion rate were 28.3% and 94.3% in TC four cycles in Japanese patients (Takabatake et al, 2009), and the incidence of FN and the completion rate in this study were 13.6% and 86.4%, respectively. There was no significant difference between these two reports.…”

“…In Japan, four cycles of TC therapy has become more common and its compliance was found to be tolerable (Takabatake et al, 2009). The PACS01 trial reported that sequential adjuvant chemotherapy with three cycles of fluorouracil, epirubicin and cyclophosphamide (FEC) followed by three cycles of docetaxel significantly improved DFS and OS , and we reported previously that the T-FEC regimen might be more tolerable than FEC followed by docetaxel in Japanese breast cancer patients (Abe et al, 2012).…”

Real-World Impact of Granulocyte-Colony Stimulating Factor on Febrile Neutropenia

“…Although the risk of fn for several chemotherapy regimens has been widely described within the context of clinical trials, only a few studies have described the occurrence of fn in clinical practice [19][20][21][22][23] . Interestingly, the reported incidence of fn associated with specific chemotherapy regimens is higher in clinical practice than in clinical trials 19,21,[23][24][25] .…”

The Cost–Utility of Adjuvant Chemotherapy Using Docetaxel and Cyclophosphamide Compared with Doxorubicin and Cyclophosphamide in Breast Cancer

“…We assumed twice the fn risk with tc than with ac and comparable base case utilities for both regimes during the treatment period. However, in clinical practice, tc chemotherapy is perhaps more commonly used in older patients and in those with node-negative disease, and it is associated with higher fn rates and possibly with lower treatment-related utility 27,[31][32][33] . Our cost-utility estimates in those practical scenarios, and in circumstances in which primary g-csf prophylaxis is considered for all patients, were less favorable than those in the primary analysis based on clinical trial data, although they remained within commonly used cost-utility thresholds 36,37 .…”

“…The base case scenario incorporated secondary prophylaxis with granulocyte colony-stimulating factor (g-csf) after fn events and assumed no chemotherapy dose adjustments. However, outside of clinical trials, use of tc appears to be associated with higher fn rates of approximately 26% (range: 10%-46%) without and 6% (range: 0%-7%) with primary g-csf prophylaxis 27,31,32,33 . Primary prophylaxis with g-csf is also sometimes used with the tc regimen in clinical practice, because it is recommended for chemotherapeutic regimens associated with a fn risk greater than 20% 34 .…”