Encouraging Results From First Trials of Platelet Growth Factor

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Oncology NEWS InternationalOncology NEWS International Vol 5 No 6
Volume 5
Issue 6

ASCO--Both forms of recombinant human platelet growth factor currently under study have been shown to enhance platelet recovery after myelosup-pressive chemotherapy without serious side effects. The first four clinical trials of the two products--pegylated megakaryocyte growth and development factor (MGDF, Amgen), which is linked to polyethylene glycol to improve its stability and half-life; and thrombopoietin (rhTPO, Genentech)--were presented at an ASCO scientific symposium.

ASCO--Both forms of recombinant human platelet growth factor currentlyunder study have been shown to enhance platelet recovery aftermyelosup-pressive chemotherapy without serious side effects. Thefirst four clinical trials of the two products--pegylated megakaryocytegrowth and development factor (MGDF, Amgen), which is linked topolyethylene glycol to improve its stability and half-life; andthrombopoietin (rhTPO, Genentech)--were presented at an ASCO scientificsymposium.

Two randomized, double-blind, placebo-controlled phase I/II trials,one in the United States and one in Australia, showed the safetyand efficacy of MGDF. In the US trial, conducted at Emory, UCLA,and Duke, MGDF (at six dose levels ranging from .03 to 5 mcg/kg/day)proved safe and well tolerated when given after carboplatin (Paraplatin)and paclitaxel (Taxol) therapy. The 53 patients had previouslyuntreated stage III or IV non-small-cell lung cancer.

Administration of multiple injections of MGDF after chemotherapyresulted in significantly faster recovery of platelet counts (median,14 days vs more than 21 days with placebo), said Michael Fanucchi,MD, associate professor of medicine, Emory University.

Post-chemotherapy platelet nadirs also were 70% higher in patientstreated with MGDF than in those given placebo (median, 189,000vs 110,000/mm³).

In the Australian trial, patients with previously treated advancedcancers were given placebo or MGDF together with G-CSF (Neupogen)either before (17 patients) or after (41 patients) therapy withcarboplatin plus cyclophosphamide.

MGDF enhanced platelet recovery in a dose-dependent manner, saidDr. G. Begley, of the Centre for Developmental Cancer Therapeutics,Parkville, Victoria. Platelet counts also nadired earlier withMGDF than with placebo. Importantly, MGDF, in doses up to 5 mcg/kg/day,was well tolerated when given with G-CSF.

Trials of rhTPO

Pretreatment with a single dose of rhTPO (0.3 to 2.4 mcg/kg/day)increased platelet counts in 18 patients with soft-tissue sarcomaor advanced cancer, said Saroj Vadhan-Raj, MD, of M.D. Anderson.She reported preliminary findings of two ongoing phase I studiesconducted at M.D. Anderson and the Cancer Therapy and ResearchCenter, San Antonio.

"A rise in platelet counts was seen in every patient whoreceived the drug," she said, adding that the effects weredose related. "Up to a threefold rise in platelet countswas seen at the highest dose level tested," she said.

In both studies, rhTPO was given as a single dose 3 weeks priorto chemotherapy. The 12 previously untreated sarcoma patientsat M.D. Anderson were given doxorubicin plus ifosfamide (Ifex),while the 6 advanced cancer patients at San Antonio received salvagethiotepa.

In the M.D. Anderson patients, platelet counts rose by an averageof 60% in those given the lowest rhTPO dose and by over 200% inthose treated with the highest dose, Dr. Vadhan-Raj said. Similartrends were seen in the patients treated in San Antonio. No majorside effects related to rhTPO were observed.

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