Phase II Clinical Study of Protection of Nail Change and Skin Toxicity by Using a Frozen Glove in Japanese Patients with Early Breast Cancer Treated by Docetaxel and Cyclophosphamide (TC) [TBCRG-03 Study].

Background: The combination docetaxel with cyclophosphamide (TC) regimen is one of standard treatment for early breast cancer patients. TC regimen has been widely used in Japan. However, a management for adverse event such as especially edema and nail/skin toxicity by docetaxel is very important due to give a completely full dosage. This multicenter phase II study was designed to evaluate the protection of nail and skin toxicity by using a frozen glove for early breast cancer patients treated by TC. Methods: Four cycles of docetaxel (75mg/m 2 ) and cyclophosphamide (600mg/m 2 ) administered intravenously (i.v.) every 21 days after surgery for primary breast cancer. All patients were attached frozen glove at right or left hand (protected hand) from 15 minutes before to 30 minutes after administration of docetaxel. The other hand (control hand) of same patient is not attached frozen glove between a administration of TC. Safety was assessed every cycle after the start of treatment. Primary endpoint is comparison the rates of nail and skin toxicity between protected and control hand. Secondary endpoints are feasibility of adjuvant TC regimen and adverse events by frozen glove in Japanese women. Results: Fifty two patients were enrolled from September 2007 to June 2008. The nail changes (grade 1 and 2) was occurred in 10 events (19.2%) and 19 events (36.5%) at protected and control hand, respectively. The skin toxicity was occurred in 14 events (26.9%, G1:8, G2:6) and 21 events (40.4%, G1:14, G2:7) at protected and control hand, respectively. The appearance of nail and skin toxicity was significantly decreased at protected hand than control hand (p=0.01). Overall, 41 patients (78%) completed the planned four cycles of TC without dose reductions or study discontinuation. One patient discontinued because of hematological toxicity defined as discontinuation by protocol. The dose reductions were necessary in 10(19%) patients because of hematological (febrile neutropenia) and non hematological toxicity by TC. Grade 3 and 4 adverse events (AEs) were neutropenia (G3:3.9%, G4:21.6%), febrile neutropenia (21.2%), fatigue (1.9%) and dermatitis (3.8%). Grade 1 or 2 AEs frequently observed (more than 20%) were dermatitis such as rash (45%, G1:29.4%, G2:15.7%), pigmentation, nausea, anorexia, disturbance of taste, tear dropping, fatigue, edema and peripheral sensory disturbance. However, there are no adverse events by frozen glove. Conclusion: TC is feasible regimen for early Japanese breast cancer patients after surgery. Frozen glove may be useful procedure which protected the nail and skin toxicity. Furthermore, it is necessary to protect the severe dermatitis due to completely performed planned TC treatment after surgery in Japan. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 808.