Mesothelioma Standard Treatment Options II

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Standard treatment options:

1. Symptomatic treatment to include drainage of effusions, chest tube pleurodesis, or thoracoscopic pleurodesis.
2. Palliative surgical resection in selected patients.
3. Palliative radiation therapy.
4. Single-agent chemotherapy. Partial responses have been reported with doxorubicin, epirubicin, mitomycin, cyclophosphamide, cisplatin, carboplatin, and ifosfamide.
5. Combination chemotherapy (under clinical evaluation). Information about ongoing clinical trials is available from the NCI Cancer.gov Website.
6. Multimodality clinical trials.
7. Intracavitary therapy. Intrapleural or intraperitoneal administration of chemotherapeutic agents (e.g., cisplatin, mitomycin, and cytarabine) has been reported to produce transient reduction in the size of tumor masses and temporary control of effusions in small clinical studies. Additional studies are needed to define the role of intra-cavitary therapy.

The safety and efficacy of pemetrexed, an antifolate, and cisplatin in chemotherapy-n aive patients with malignant mesothelioma who were not eligible for curative surgery was demonstrated in a large phase III randomized trial. This trial compared pemetrexed (500 mg/m²) and cisplatin (75 mg/m² on day 1) with cisplatin alone (75 mg/m² on day 1 intravenously every 21 days). A total of 456 patients were enrolled: 226 patients received pemetrexed plus cisplatin and 222 patients received cisplatin alone; 8 patients did not receive therapy. After 117 patients had enrolled, folic acid and vitamin B₁₂ were added to reduce toxic effects. Folic acid (350-1,000 µg orally) was given daily, beginning 1 to 3 weeks before the first chemotherapy dose and continuing daily until 1 to 3 weeks after treatment ended. A vi tamin B₁₂ injection (1,000 µg intramuscularly ) was administered 1 to 3 weeks before the first chemotherapy dose and was repeated approximately every 9 weeks until treatment ended. Dexamethasone (4 mg) or an equivalent corticosteroid was administered orally twice daily for skin rash prophylaxis to all patients 1 day before, on the day of, and 1 day after each pemetrexed dose.

In an analysis of all patients who were randomized and treated, the combination of pemetrexed and cisplatin was associated with a statistically significant improvement in survival compared with cisplatin alone; the median survivals were 1 2.1 versus 9.3 months, respectively (P=.020). The hazard ratio for death of patients in the pemetrexed plus cisplatin arm versus those in the control arm was 0.77. Median time to progression was significantly longer in the pemetrexed plus cisplatin arm (5.7 months vs 3.9 months, P=.001). This superiority in the combination arm was also demonstrated in the vitamin supplemented subgroup. The median survivals were 13.3 and 10.0 months in the combination group and cisplatin alone group, respectively (P=.051). The principal adverse effects of the pemetrexed plus cisplatin regimen were myelosuppression, fatigue, nausea, vomiting, and dyspnea. Most grade 3 to 4 adverse effects were significantly reduced by vitamin supplem entation without any decrease in efficacy.

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