ORIGINAL ARTICLEFirst-line chemotherapy with docetaxel and cisplatin in metastatic breast cancer
Introduction
Even after adequate loco-regional treatment and systemic adjuvant polychemotherapy at the time of diagnosis, metastatic relapses occur in 40% of patients with breast cancer.1 The increasingly frequent use of anthracyclines in adjuvant treatment has led to a limitation of their use in relapsing patients. A need has therefore emerged for active nonanthracycline-containing regimens. Among the novel chemotherapeutic drugs introduced in the last decade, docetaxel (DOC) has emerged as a promising compound with remarkable activity when given alone as first-line treatment.2, 3, 4, 5
Cisplatin (CDDP) as a single agent is very active as first-line treatment in metastatic breast cancer (MBC), with response rates of 47–54%.6, 7, 8 On the basis of the reports in the relatively small literature, it can be argued that CDDP is the third most active agent in this disease, after taxanes and doxorubicin, but the relative severity of toxicity limits its use in routine clinical practice.9
Like others, we have shown that regimens combining CDDP with vinorelbine, when used as second-line treatment in MBC, are well tolerated and effective in patients who have been pretreated with anthracyclines10 and docetaxel.11 In vitro studies suggest a powerful synergy between platinum complexes and docetaxel and between platinum complexes and trastuzumab.12 These data, together with the widespread use of anthracyclines in adjuvant therapy suggest one possible role for platinum-containing regimens early in the treatment of MBC. Docetaxel is widely used after failure with anthracyclines, and preliminary data indicate a high antitumor activity of combined DOC/CDDP in this group of patients. The regimen has been found to be very active in the neoadjuvant setting, with acceptable toxicity.13
Based on preliminary data,14, 15, 16, 17 this study assessed the antitumor activity and tolerance of DOC 75 mg/m2 on day 1, followed by CDDP 75 mg/m2 on day 2, as first-line treatment in chemonaive patients with MBC. Recombinant human granulocyte colony-stimulating factor (rHuG-CSF) was given prophylactically against neutropenia because severe neutropenia has been observed in earlier studies.18
Section snippets
Inclusion criteria
The inclusion criteria applied were age 18–72 years; WHO performance status <3; histologically confirmed breast cancer that had relapsed after prior adjuvant therapies; previous hormonal and radiation therapies for advanced disease (discontinued at least 4 weeks before entry on study); metastatic disease at the time of presentation, with at least one bidimensionally measurable lesion and defined index lesions >1 cm in size found on physical examination or X-ray, or ⩾2 cm found on ultrasound or
Results
Patients’ characteristics are shown in Table 1. Of 51 patients enrolled in this trial, 50 were evaluable for response and toxicity (1 patient dropped out after the first cycle). The median age of the patients was 56 years (range 31–72). All evaluable patients together received a total of 265 treatment cycles. The mean number of treatment cycles was 5.3 per patient (range 1–8). The evaluable patients were made up of 48 women and 2 men with MBC. The median time lapse from primary diagnosis to
Discussion
This study describes the first fully published experience of docetaxel 75 mg/m2 and cisplatin 75 mg/m2 in combination as first-line chemotherapy in MBC.
In our study, 68% of patients achieved an overall response. Almost one-fifth of the patients who responded at all achieved a CR. The ratio of CR to PR was about 1:4. CRs occurred in patients with low tumor burden and in those with soft tissue and/or lung disease. Nineteen (61%) of the 31 patients with visceral involvement responded.
The median
References (28)
- et al.
A multicentre phase II study of the efficacy and safety of docetaxel as first-line treatment of advanced breast cancerReport of the Clinical Screening Group of the EORTC
Ann Oncol
(1996) Platinum compounds in the treatment of advanced breast cancer
Clin Breast Cancer
(2001)The platinum agentsa role in breast cancer treatment?
Semin Oncol
(2001)- et al.
Vinorelbine and cisplatin in metastatic breast cancer patients previously treated with anthracyclines
Ann Oncol
(2000) - et al.
Docetaxel–cisplatin combination (DC) chemotherapy in patients with anthracyclines- resistant advanced breast cancer
Ann Oncol
(1999) Polychemotherapy for early breast canceran overview of the randomized trials
Lancet
(1998)- et al.
A multicentre phase II study of docetaxel 75 mg/m2 as first-line chemotherapy for patients with advanced breast cancerreport of the Clinical Screening Group of the EORTC. European Organization for Research and Treatment of Cancer
Br J Cancer
(1996) - et al.
Phase II and pharmacologic study of docetaxel as initial chemotherapy for metastatic breast cancer
J Clin Oncol
(1996) - et al.
Docetaxel in patients with metastatic breast cancera phase II study of the National Cancer Institute of Canada—Clinical Trials Group
J Clin Oncol
(1996) - et al.
Cisplatin as first-line therapy for metastatic breast cancer
J Clin Oncol
(1988)
CAP (cyclophosphamide, Adriamycin, cisplatinum) in the treatment of advanced breast cancer
Neoplasma
Vinorelbine and cisplatin for metastatic breast cancera salvage regimen progressing after docetaxel and anthracyclines treatment
Cancer Invest
Trastuzumab and chemotherapeuticsdrug interactions and synergies
Semin Oncol
Phase II trial of neo-adjuvant docetaxel and cisplatin for the treatment of locally advanced breast cancer
Proc Am Soc Clin Oncol
Cited by (43)
Conjugated linoleic acid strengthens the apoptotic effect of cisplatin in A549 cells
2023, Prostaglandins and Other Lipid MediatorsCamouflaged liposomes by 11A4-nanobody for co-delivery of cisplatin and nitroxoline in breast cancer tumors: An in vitro/in vivo study
2022, Journal of Drug Delivery Science and TechnologyCitation Excerpt :It generally binds with DNA to create DNA lesions, block the production of DNA, mRNA, and proteins, arrest DNA replication, cause DNA damage, and subsequently induce apoptosis in cancer cells [22]. Cisplatin has been used concomitantly with other cytotoxic drugs for the treatment of breast cancer such as docetaxel [23], doxorubicin [24], gemcitabine [25], and 5-fluorouracil [26] and has shown desirable anticancer effects; however, usage of two cytotoxic drugs in combination may increase the incidence of severe adverse effects. Cathepsin B, a lysosomal cysteine papain-like protease, plays many key roles at different stages of malignant progression [27].
PEG-PCL based micelle hydrogels as oral docetaxel delivery systems for breast cancer therapy
2014, BiomaterialsCitation Excerpt :Docetaxel has been approved as a first-line drug in the treatment of breast cancer in clinical [1,2].