A phase II study of GM-CSF and rIFN-γ1b plus carboplatin for the treatment of recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer

Abstract

Objective To evaluate the efficacy and toxicity of carboplatin, granulocyte-macrophage colony-stimulating factor (GM-CSF) and recombinant interferon gamma 1b (rIFN-γ1b) in women with recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer. Methods In this phase II study, patients with recurrent, platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer were treated with subcutaneous GM-CSF and rIFN-γ1b before and after intravenous carboplatin until disease progression or unacceptable toxicity. All patients had measurable disease and a chemotherapy-free interval ≥6 months. Response was determined using RECIST criteria and CA 125 levels. Results Between 2003 and 2007, 59 patients received a median of 6 cycles of therapy (range, 1 to 13 cycles). Median age at enrollment was 61 years (range, 35 to 79 years). Median time to progression prior to enrollment was 11 months (range, 6 to 58 months). Of 54 patients evaluable for response, 9 (17%) had a complete response, 21 (39%) had a partial response, and 24 (44%) had progressive disease. The overall response rate was 56% (95% CI: 41% to 69%). With a median follow-up of 6.4 months, median time to progression was 6 months. Myeloid derived cells and platelets increased on day 9 of each chemotherapy cycle. The most common adverse effects were bone marrow suppression, carboplatin hypersensitivity, and fatigue. Responders reported improved quality of life. Conclusion This pre and post-carboplatin cytokine regimen resulted in a reasonable response and a hematologic profile that could invite further evaluation of its components in the treatment of patients with ovarian cancer.

Immunotherapy in ovarian cancer

“…25 GM-CSF was also evaluated in combination with recombinant interferon gamma 1b (rIFN-γ 1b) in a phase II trial of women with recurrent, platinum-sensitive ovarian, fallopian tube and primary peritoneal cancer. 26 In this cohort of 59 patients, GM-CSF and rIFN-γ 1b in combination with carboplatin produced a response rate of 56%. 26 In summary, cytokine immunotherapy has demonstrated promising results in ovarian cancer patients.…”

“…26 In this cohort of 59 patients, GM-CSF and rIFN-γ 1b in combination with carboplatin produced a response rate of 56%. 26 In summary, cytokine immunotherapy has demonstrated promising results in ovarian cancer patients. However, these results need to be interpreted with caution due to the heterogeneity often also expressed by normal cells, creating limitations for their use.…”

Hypoxia-specific GM-CSF-overexpressing neural stem cells improve graft survival and functional recovery in spinal cord injury

“…25 Recently, GM-CSF has been suggested to promote survival of dopaminergic neurons in a murine model of Parkinson's disease, 13 and has even been thought to stimulate axonal outgrowth in paraplegic rats. 14 Although GM-CSF is commercially available and widely used for treating some types of cancer as a vaccine adjuvant, 26,27 the therapeutic evaluation of GM-CSF within the hypoxic injured spinal cord has not been investigated. Here, we used GM-CSF overexpression in hypoxic conditions (Figure 2) to observe its possible neuroprotective effects in vitro (Figures 3 and 4) and in vivo ( Figure 5).…”

Particle platforms for cancer immunotherapy

“…39 GM-CSF both stimulates differentiation of myeloid precursors towards the DC lineage and functions as a chemoattractant, luring DCs to either the tumor or the site of antigen deposition. Clinical use of GM-CSF has been shown to be safe and effective.…”