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PubMed2002

Treatment of aggressive non-Hodgkin's lymphoma with chemotherapy in combination with filgrastim.

Non-Hodgkin's lymphoma (NHL) is one of the ten most common cancers in the developed world. The incidence has increased significantly over the past two decades and it is a particular burden in patients over the age of 60 years. The gold standard for primary treatment of aggressive NHL is combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). Haematological growth factors, such as granulocyte colony-stimulating factor (G-CSF), can be used to ameliorate chemotherapy-induced neutropenia, thus facilitating delivery of chemotherapy at the planned dose intensity. The International Prognostic Index is able to identify high-risk patients who are unlikely to be cured with standard primary chemotherapy. In these patients, the use of dose-intensive therapy, including high-dose chemotherapy with stem cell support, is being evaluated as potential primary therapy. Stem cell transplantation is currently the treatment of choice for patients with relapsed NHL or those with chemosensitive refractory disease. Autologous peripheral blood stem cells mobilised into the circulation by G-CSF help achieve rapid haematological reconstitution and are now the preferred source of stem cells over bone marrow for this form of therapy. G-CSF is also used to support allogeneic transplantation, which exerts a therapeutic graft-versus-lymphoma effect. Administration of G-CSF following autologous or allogeneic peripheral blood stem cell transplantation accelerates neutrophil recovery.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Phase I trial of paclitaxel, carboplatin, and topotecan with or without filgrastim (granulocyte-colony stimulating factor) in the treatment of patients with advanced, refractory cancer.

BACKGROUND: Topotecan is a new antineoplastic agent with a broad spectrum of activity. The purpose of this Phase I trial was to define the maximum tolerated dose of topotecan when added to the widely used combination of paclitaxel and carboplatin. METHODS: Patients with advanced cancer that was refractory or resistant to standard treatments were treated with paclitaxel, carboplatin, and topotecan; doses were escalated in sequential cohorts of patients. After definition of the maximum tolerated dose without cytokines, granulocyte-colony stimulating factor (G-CSF) was added and further dose escalation was attempted. RESULTS: The maximum tolerated doses were: paclitaxel, 135 mg/m2, as a 1-hour intravenous (i.v.) infusion on Day 1; carboplatin, area under the curve 5.0, on Day 1; and topotecan, 0.75 mg/m2, i.v. on Days 1, 2, and 3; the regimen was repeated every 21 days. Myelosuppression, particularly thrombocytopenia, was the dose-limiting toxicity with this three-drug combination. Nonhematologic toxicity was uncommon. The addition of G-CSF did not allow substantial dose escalation because thrombocytopenia was uneffected by this agent. Eleven of 25 patients had major responses to this combination, including 8 of 14 patients with previously treated small cell lung carcinoma. CONCLUSIONS: The combination of paclitaxel, carboplatin, and topotecan is feasible, although only relatively low doses of all three drugs can be tolerated due to myelosuppression. This regimen showed a high level of activity in these patients with refractory cancer, and merits further investigation.

Adult↗
PubMed1995

Allogeneic peripheral blood progenitor cells mobilized by G-CSF (filgrastim) for a second transplant in a patient with acute myeloid leukemia in relapse.

A 25-year-old man with AML, who relapsed 21 months after his first allogeneic bone marrow transplant (BMT), underwent a second transplant with peripheral blood progenitor cells (PBPC) obtained from his HLA-identical sibling. The donor cells were collected through four aphereses after G-CSF mobilization with 5 micrograms/kg/d for 5 days. The patient received BAVC conditioning regimen followed by non-T cell-depleted PBPC. Successful engraftment occurred with rapid hematopoietic recovery (time to reach 0.5 x 10(9)/L neutrophils and 50 x 10(9) platelets/L was 15 and 19 days, respectively). A bone marrow aspirate on day +19 showed trilineage engraftment. Erythrocyte phenotype showed that erythropoiesis was of donor origin. The patient developed grade II acute GVHD that responded to prednisone. Seven months after PBPC transplantation he remains in complete remission, alive and well, with just limited chronic GVHD. Allogeneic peripheral blood progenitor cell transplantation may be considered a suitable alternative to marrow transplant.

Acute Disease↗