Hematological side-effect profiles of individualized chemotherapy regimen for recurrent ovarian cancer.

The long-term results for patients with recurrent ovarian cancer (ROC) are poor. There is a need to optimize treatment strategies to improve outcome by avoiding ineffective regimens which are often associated with exacerbated side-effects. Individualized chemotherapy regimens guided by a chemosensitivity assay (ATP-tumor chemosensitivity assay) have already been used successfully to direct chemotherapy. Taking the results of this assay into account, application of drug combinations appears more advisable. Here we present a systematic evaluation of toxicities seen with individualized chemotherapy for ROC. A total of 62 patients who received 314 cycles of antineoplastic therapies were evaluated. Three single agents (topotecan, paclitaxel and gemcitabine) and five combinations (cisplatin/gemcitabine, carbopatin/gemcitabine, gemcitabine/treosulfan, mitoxantrone/paclitaxel and carboplatin/paclitaxel) were examined. With respect to myelotoxicity, most single agents except topotecan revealed favorable results in comparison to drug combinations. However, this observation lacks statistical significance. Generally, severe myelosuppression was rare. The highest incidence of leukopenia was seen in regimens with mitoxantrone/paclitaxel or gemcitabine/treosulfan, respectively. Thrombocytopenia accompanied most commonly a topotecan therapy. In the present study combination regimens tend to be more toxic than monotherapies. When response rates are comparable, empirically chosen treatment combination therapies should only be practiced in carefully planned clinical studies.

A phase II study of dose-dense docetaxel and mitoxantrone in the treatment of patients with high-risk metastatic breast cancer.

Doxetaxel (DCT) and mitoxantrone (MX) are highly active and potentially synergistic agents in the treatment of metastatic breast cancer (MBC). This pilot study evaluates the combination of dose-dense DCT and MX in patients with MBC to determine the efficacy and toxicity of this therapy. Thirty-six patients (56.1+/-1.7 years) were studied. The patients received DCT (35 mg/m(2) q1w) and MX (6 mg/m(2) q2w) for 6 weeks of an 8-week interval. Patients with tumor response or stable disease (SD) continued the treatment for a maximum of two additional periods. Hematologic and non-hematologic parameters were determined using the WHO common toxicity score. During this study 14 patients (40%) experienced partial response, 14 (40%) SD. In 20% of the cases the disease progressed on therapy. The treatment with DCT and MX was well tolerated. Seventeen patients (47%) experienced grade 3 leukopenia. Other hematologic and non-hematologic side effects did not exceed grade 2. One patient died during therapy because of a pulmonary embolism, which was unlikely related to active agents. Dose-dense DCT and MX combines both clinical activity and convenience for the patient. Therefore, we conclude that this regimen is a promising therapy in MBC, which warrants confirmation by large-scale clinical trials.