Combination of Docetaxel and Doxorubicin as First-Line Chemotherapy in Metastatic Breast Cancer

Abstract

Docetaxel (Taxotere) and doxorubicin have previously demonstrated a significant antitumor activity in patients with metastatic breast cancer. Furthermore, a lack of cross resistance and overlapping toxicities between the two agents have been reported. In a prospective study, docetaxel (80 mg/m2, 1-hr iv infusion) and doxorubicin (60 mg/m2, 1-hr iv infusion) were administered as first-line chemotherapy in metastatic breast cancer patients to evaluate the clinical efficacy and toxicity of the combination. Forty-three patients were enrolled in the study. The median age was 47 years (range, 30-69). The docetaxel-doxorubicin combination was applied with 3-week intervals until progression. Complete response was achieved in 9 (21.4%) of 42 assessable patients and partial response in 24 (57.2%) patients, for an overall response rate of 78.6%. Median response duration was 8 months (3-18 months). Nausea and vomiting (76%), alopecia (64%), neutropenia (35.7%) and mucositis (33%) were the major side effects of the combination. There was one case of cardiac toxicity. In conclusion, the docetaxel-doxorubicin protocol can be considered as an active regimen for the treatment of patients with metastatic breast cancer with acceptable toxicity and a fairly high response rate.

Perspectives on cancer therapy-induced mucosal injury

“…The incidence of oral and GI mucositis varied significantly among different treatment regimens and modalities (Table 4). 60–398 Most anthracycline‐based regimens were associated with rates of oral mucositis in the 1–10% range, except when regimens included 5‐FU. Included among these are the standard regimens for adjuvant therapy in patients with breast cancer (5‐FU, doxorubicin, and cyclophosphamide; doxorubicin and cyclophosphamide; or 5‐FU, epirubicin, and cyclophosphamide) as well as regimens for patients with non‐Hodgkin lymphomas, including cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP).…”

Kaempferol and docetaxel diminish side population and down-regulate some cancer stem cell markers in breast cancer cell line MCF-7

“…Although cisplatin-based chemotherapy regimen has been used for treatment of numerous human cancers including bladder, head and neck, lung, ovarian, and testicular, enrichment of CSCs after cisplatin treatment have been seen in many cancers that lead to relapse and decreased overall survival of patients (Shafee et al, 2008;Wang et al, 2017). As other examples, however, combination of docetaxel and doxorubicin, as well as tamoxifen, are widely used as first-line chemotherapy in treatment of breast cancers, but the percentage of breast CSCs was not decreased after treatment with these common chemotherapy drugs (Baltali et al, 2001). In addition to resistance of cancer cells to chemotherapy drugs, toxicity of these agents to normal tissues and their side effects have motivated researcher to look for new therapeutic approaches.…”

“…Although docetaxel (Taxotere) and doxorubicin (Adriamycin) have previously shown a significant antitumor activity in breast cancer patients, recurrence of many of them shows their resistance to chemotherapy (Baltali et al, 2001). Therefore, finding new strategies to target breast CSCs can create new hope for treatment.…”

Phase II multicentre randomised study of docetaxel plus epirubicin vs 5-fluorouracil plus epirubicin and cyclophosphamide in metastatic breast cancer

“…Overall response rates of 57 -79% were reported with 3-weekly combinations of docetaxel 60 -80 mg m À2 in five first-line noncomparative studies in a total of 170 patients with metastatic breast cancer (Sparano et al, 2000;Baltali et al, 2001;Lippe et al, 2002;Aihara et al, 2003;Morales et al, 2004). Previous noncomparative studies of 3-weekly epirubicin 75 mg m À2 plus docetaxel 75 mg m À2 have yielded overall tumour response rates of 67 -84%, with overall survival of up to approximately 2 years (Airoldi et al, 2001;Yeo et al, 2002;Morales et al, 2004).…”

“…Haematologic adverse events (most notably neutropenia) were most common, with no excessive cardiac toxicity or any indication that the addition of docetaxel to doxorubicin increases the cardiotoxicity of the latter (Sparano et al, 2000;Baltali et al, 2001;Lippe et al, 2002;Aihara et al, 2003;Morales et al, 2004). In one phase II noncomparative trial of epirubicin and docetaxel, no grade 4 nonhaematologic adverse events and very low levels of cardiotoxicity (reversible congestive heart failure in one of 60 patients only) were observed (Yeo et al, 2002), whereas in another study there was no grade 3 -4 cardiac toxicity and no treatment-related mortality among 46 patients (Airoldi et al, 2001).…”