Purpose

Current guidelines recommend prophylactic use of granulocyte-colony stimulating factors (G-CSF) when febrile neutropenia (FN) risk is greater than 20%. Advanced age is a risk factor for FN; however, little is known about the impact of other factors on the incidence of FN in an older population.

Patients and methods

We analyzed SEER-Medicare data (1994-2005) to develop and validate a prediction model for hospitalization with fever, infection, or neutropenia occurring after chemotherapy initiation for patients with breast, colorectal, prostate, and lung cancer.

Results

In multivariate analysis (N = 58,053) independent predictors of FN included advanced stage at diagnosis [stage 2 (OR 1.29; 95% CI: 1.09-1.53), stage 3 (1.38; 95% CI: 1.19-1.60), and stage 4 (1.57; 95% CI: 1.35-1.83)], number of associated comorbid conditions [one condition (1.13; 95% CI: 1.02-1.28), two conditions (1.39; 95% CI: 1.22-1.57), and three or more conditions (1.81; 95% CI: 1.61-2.04)], receipt of myelosuppressive chemotherapy (1.11; 95% CI: 0.94-1.32), and receipt of chemotherapy within 1 month of diagnosis [1 to 3 months (0.70; 95% CI: 0.62-0.80) and greater than 3 months (0.63; 95% CI: 0.55-0.73)].

Conclusion

We created a prediction model for febrile neutropenia with first cycle of chemotherapy in a large population of elderly patients with common malignancies.

OBJECTIVES: Dichloroacetate (DCA) is a highly bioavailable small molecule that inhibits pyruvate dehydrogenase kinase, promoting glucose oxidation and reversing the glycolytic phenotype in preclinical cancer studies. We designed this open-label phase II trial to determine the response rate, safety, and tolerability of oral DCA in patients with metastatic breast cancer and advanced stage non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: This trial was conducted with DCA 6.25 mg/kg orally twice daily in previously treated stage IIIB/IV NSCLC or stage IV breast cancer. Growth inhibition by DCA was also evaluated in a panel of 54 NSCLC cell lines with and without cytotoxic chemotherapeutics (cisplatin and docetaxel) in normoxic and hypoxic conditions. RESULTS AND CONCLUSIONS: Under normoxic conditions in vitro, single-agent IC50 was >2 mM for all evaluated cell lines. Synergy with cisplatin was seen in some cell lines under hypoxic conditions. In the clinical trial, after seven patients were enrolled, the study was closed based on safety concerns. The only breast cancer patient had stable disease after 8 weeks, quickly followed by progression in the brain. Two patients withdrew consent within a week of enrollment. Two patients had disease progression prior to the first scheduled scans. Within 1 week of initiating DCA, one patient died suddenly of unknown cause and one experienced a fatal pulmonary embolism. We conclude that patients with previously treated advanced NSCLC did not benefit from oral DCA. In the absence of a larger controlled trial, firm conclusions regarding the association between these adverse events and DCA are unclear. Further development of DCA should be in patients with longer life expectancy, in whom sustained therapeutic levels can be achieved, and potentially in combination with cisplatin.

Objectives

Dichloroacetate (DCA) is a highly bioavailable small molecule that inhibits pyruvate dehydrogenase kinase, promoting glucose oxidation and reversing the glycolytic phenotype in preclinical cancer studies. We designed this open-label phase II trial to determine the response rate, safety, and tolerability of oral DCA in patients with metastatic breast cancer and advanced stage non-small cell lung cancer (NSCLC).

Materials and methods

This trial was conducted with DCA 6.25 mg/kg orally twice daily in previously treated stage IIIB/IV NSCLC or stage IV breast cancer. Growth inhibition by DCA was also evaluated in a panel of 54 NSCLC cell lines with and without cytotoxic chemotherapeutics (cisplatin and docetaxel) in normoxic and hypoxic conditions.

Results and conclusions

Under normoxic conditions in vitro, single-agent IC50 was >2 mM for all evaluated cell lines. Synergy with cisplatin was seen in some cell lines under hypoxic conditions. In the clinical trial, after seven patients were enrolled, the study was closed based on safety concerns. The only breast cancer patient had stable disease after 8 weeks, quickly followed by progression in the brain. Two patients withdrew consent within a week of enrollment. Two patients had disease progression prior to the first scheduled scans. Within 1 week of initiating DCA, one patient died suddenly of unknown cause and one experienced a fatal pulmonary embolism. We conclude that patients with previously treated advanced NSCLC did not benefit from oral DCA. In the absence of a larger controlled trial, firm conclusions regarding the association between these adverse events and DCA are unclear. Further development of DCA should be in patients with longer life expectancy, in whom sustained therapeutic levels can be achieved, and potentially in combination with cisplatin.