Docetaxel, cyclophosphamide, and trastuzumab as neoadjuvant chemotherapy for HER2-positive primary breast cancer

Nakatsukasa, Katsuhiko; Koyama, Hiroshi; Oouchi, Yoshimi; Imanishi, Seiichi; Mizuta, Naruhiko; Sakaguchi, Kouichi; Fujita, Yoshifumi; Imai, A.; Okamoto, Akiko; Hamaoka, Asako; Soushi, Mari; Fujiwara, Ikuya; Kotani, Tomoya; Matsuda, Takayuki; Fukuda, Kenichirou; Morita, Midori; Kawakami, Sadao; Kadotani, Yayoi; Konishi, Eiichi; Yanagisawa, Akio; Goto, Mariko; Yamada, Kazutaka; Taguchi, Tetsuya

doi:10.1007/s12282-016-0677-4

Cited by 14 publications

(22 citation statements)

References 20 publications

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“…Considering that only a small proportion of patients with Her2-positive status were treated with trastuzumab in the neoadjuvant setting, the pCR rate of Her2-positive patients in our study was not so high as in studies with trastuzumab-based NAC. 31 …”

Section: Discussionmentioning

confidence: 99%

Peripheral inflammation/immune indicators of chemosensitivity and prognosis in breast cancer patients treated with neoadjuvant chemotherapy

Qian¹,

Ji²,

Li³

et al. 2018

OTT

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IntroductionNeoadjuvant chemotherapy (NAC) has become a standard treatment for locally advanced breast cancer. The present study was designed to investigate the predictive value of different peripheral inflammation/immune biomarker responses to NAC and prognosis in breast cancer patients.Materials and methodsA total of 180 breast cancer patients treated with NAC in the First Affiliated Hospital with Nanjing Medical University between January 2008 and March 2015 were enrolled in the study. The associations between inflammation/immune indicators and pathological complete response (pCR) were determined, and the prognostic value of inflammation/immune indicators was also evaluated.ResultsIn the univariate analysis, patients with a high pretreatment peripheral lymphocyte count (.2.06×109/L) showed a higher pCR rate than those with a low lymphocyte count (23.9% vs 10.4%, P=0.023). The pCR rate of patients with a neutrophil: lymphocyte ratio ≤2.15 was significantly higher than that of patients with a high neutrophil: lymphocyte ratio (20% vs 7.8%; P=0.03). However, multivariate analysis revealed that only the high lymphocyte count was predictive for pCR (odds ratio: 4.375, 95% CI: 1.429–13.392, P=0.010). In the survival analysis, patients with a higher neutrophil count (.2.65×109/L) were confirmed to have a shorter disease-free survival (hazard ratio: 4.322, 95% CI: 1.028–18.174, P=0.046), and the high neutrophil count was significantly associated with lymphovascular invasion (P=0.037).ConclusionWe demonstrated that a high level of baseline peripheral lymphocyte count can be a predictor for high efficacy of NAC for breast cancer patients, and low baseline peripheral neutrophil count may contribute to the favorable disease-free survival.

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Section: Discussionmentioning

confidence: 99%

Peripheral inflammation/immune indicators of chemosensitivity and prognosis in breast cancer patients treated with neoadjuvant chemotherapy

Qian¹,

Ji²,

Li³

et al. 2018

OTT

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“…The objective of our study was to evaluate the efficacy of prophylactic anti-allergic drug administration against TC-related skin eruption in patients with primary breast cancer. This study is a subanalysis of data that we previously reported as part of a combined phase 2 study of TC NAC and HER-TC NAC [3,4]. This study was an openlabel, nonrandomized study, which was conducted at seven different institutions.…”

Section: Methodsmentioning

confidence: 99%

“…The cumulative incidence of skin eruption every chemotherapy cycle is summarized in Figure 3. As shown in Figure 3, the onset of skin efficacy and tolerability of TC neoadjuvant chemotherapy (NAC) and HER-TC NAC in patients with breast cancer in previous studies [3,4]. Therefore, in this work, we re-analyzed the data from those studies to retrospectively evaluate the prophylactic effectiveness of anti-allergic drugs against TC/HER-TC-related skin eruption among the patients in our clinical trial.…”

Section: Skin Toxicitiesmentioning

confidence: 99%

Prophylactic Anti-allergic Drug Administration to Prevent Docetaxel and Cyclophosphamide-induced Skin Toxicity: Sub-analysis of a Multiinstitution Neoadjuvant Chemotherapy Trial in Primary Breast Cancer Patients

Nakatsukasa¹,

Koyama²,

Ouchi³

et al. 2018

J Can Sci Res

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TC and HER-TC are well known to cause skin eruption, indicating that they have a degree of non-hematological toxicity. However, the cause of this toxicity is unclear, and reliable treatment methods have not yet been established. As a result, prophylactic methods to prevent TC/ HER-TC-related skin eruption are urgently needed. Anti-allergic drugs are sometimes administered to treat skin eruption, but their prophylactic effectiveness has not yet been investigated. We hypothesized that the prophylactic use of anti-allergic drugs would decrease the incidence of TC/HER-TC-related skin eruption. We have already reported the

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“…[5][6][7] A combination of docetaxel and cyclophosphamide are used as neoadjuvant chemotherapy in HER2-negative primary breast cancer and a combination of docetaxel, cyclophosphamide, and trastuzumab as neoadjuvant chemotherapy for HER2-positive primary breast cancer. 8,9 In most cases, cyclophosphamide may damage the immune function of cancer patients, and this may lead to invasive fungal infections (IFIs). Besides, chemotherapy regimens that include cyclophosphamide have a >20% incidence of febrile neutropenia, and this will put patients at higher risk of developing IFIs.…”

Section: Introductionmentioning

confidence: 99%

The Influence of Different Triazole Antifungal Agents on the Pharmacokinetics of Cyclophosphamide

et al. 2020

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Background: Cyclophosphamide is one of the most important chemotherapeutic drugs. Known as a widely accepted treatment strategy, chemotherapy may damage the immune function of cancer patients; as a result, invasive fungal infections (IFIs) occur. Triazole antifungal agents are the most acceptable drugs for IFI treatment, especially those infections caused by chemotherapy. Objective: We aimed to investigate the effects of different triazole antifungal drugs, including fluconazole, itraconazole, and ketoconazole, on the pharmacokinetics (PK) of cyclophosphamide. In addition, we also characterize the potential drug-drug interactions (DDIs) between cyclophosphamide and various triazole antifungal drugs. Methods: The necessary pharmacokinetic parameters and physicochemical data were obtained from published studies. Physiologically based pharmacokinetic (PBPK) models were developed and validated in virtual subjects using Simcyp software. The validated PBPK models were used to evaluate potential DDIs between cyclophosphamide and different triazole antifungal agents in cancer patients. Triazole antifungal agents were simulated by oral administration, whereas cyclophosphamide was simulated by intravenous administration. Results: Simulated plasma concentration-time curves of fluconazole, itraconazole, ketoconazole, and cyclophosphamide were in good consistency with the observed profiles. Our results suggested that the pharmacokinetic parameters of cyclophosphamide were increased by various extents when coadministered with different triazole antifungals. The area under the plasma concentration-time curve of cyclophosphamide was increased when combined with fluconazole, itraconazole, or ketoconazole. Conclusions and Relevance: Ketoconazole had the greatest effect on the PK of cyclophosphamide among the 3 triazole antifungals. Our study provides clues that the toxicity and adverse drug reactions that are associated with cyclophosphamide should be closely monitored when coadministered with ketoconazole.

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Docetaxel, cyclophosphamide, and trastuzumab as neoadjuvant chemotherapy for HER2-positive primary breast cancer

Abstract: Four cycles of HER-TC may be a NAC option for HER2-positive breast cancer.

Cited by 14 publications

References 20 publications

Peripheral inflammation/immune indicators of chemosensitivity and prognosis in breast cancer patients treated with neoadjuvant chemotherapy

Peripheral inflammation/immune indicators of chemosensitivity and prognosis in breast cancer patients treated with neoadjuvant chemotherapy

Prophylactic Anti-allergic Drug Administration to Prevent Docetaxel and Cyclophosphamide-induced Skin Toxicity: Sub-analysis of a Multiinstitution Neoadjuvant Chemotherapy Trial in Primary Breast Cancer Patients

The Influence of Different Triazole Antifungal Agents on the Pharmacokinetics of Cyclophosphamide

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