Interferon Alpha and Metronomic Cyclophosphamide for Metastatic Kidney Cancer: A Phase 2 Study

Abstract

Metronomic chemotherapy has been tested only a few times in the treatment of metastatic kidney cancer. We have combined metronomically dosed cyclophosphamide (mCTX) with full dosed interferon alpha (IFN) in patients with disseminated clear cell cancer. Toxicity was mainly attributable to IFN treatment. We have noticed mainly hematological and general symptoms with only few grade 3 or 4 adverse events. No patient required mCTX withdrawal. In 30 patients evaluated for the response, clinical benefit (CB) (objective responses and stabilization of the disease ≥24 weeks) was observed in 40%. Median overall survival (OS) for the whole group was 13.2 months. Survival responders and nonresponders were 9.5 versus 28.9 months (P=0.001). Patients with a higher hemoglobin concentration and fibrinogen level <6 g/L had a higher probability of response. Responders also had different kinetics of fibrinogen than nonresponders. When assessed for clinical response, the combination of mCTX and IFN proved to be disappointing. In contrast, OS in patients with CBs proved to be long. It is crucial to properly select patients for whom some predictive markers can be used. The combination of metronomic chemotherapy with targeted therapies might be an interesting direction for further research.

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

“…Grade 4 toxicity was seen in 48.8% [173]. In a recent trial by Tupikowski et al metronomic CP and interferon α combination resulted in a CB longer than 24 weeks, which was observed in 40% in 30 patients; median OS was 13.2 months [174].…”

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

“…Grade 4 toxicity was seen in 48.8% [173]. In a recent trial by Tupikowski et al metronomic CP and interferon α combination resulted in a CB longer than 24 weeks, which was observed in 40% in 30 patients; median OS was 13.2 months [174].…”

The Nitrogen Mustards

“…IFN-a was given three times per week on a 4-week cycle and 50 mg oral cyclophosphamide was administered daily from day 2 of each cycle. A CBR of 40% and a median OS of 13.2 months was observed (Tupikowski et al, 2015).…”

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

“…Grade 4 toxicity was seen in 48.8% [173]. In a recent trial by Tupikowski et al metronomic CP and interferon α combination resulted in a CB longer than 24 weeks, which was observed in 40% in 30 patients; median OS was 13.2 months [174].…”

The Nitrogen Mustards

“…IFN-a was given three times per week on a 4-week cycle and 50 mg oral cyclophosphamide was administered daily from day 2 of each cycle. A CBR of 40% and a median OS of 13.2 months was observed (Tupikowski et al, 2015).…”

Metronomic Chemotherapy: A Systematic Review of the Literature and Clinical Experience

“…Grade 4 toxicity was seen in 48.8% [173]. In a recent trial by Tupikowski et al metronomic CP and interferon α combination resulted in a CB longer than 24 weeks, which was observed in 40% in 30 patients; median OS was 13.2 months [174].…”

The Nitrogen Mustards

“…IFN-a was given three times per week on a 4-week cycle and 50 mg oral cyclophosphamide was administered daily from day 2 of each cycle. A CBR of 40% and a median OS of 13.2 months was observed (Tupikowski et al, 2015).…”