ABSTRACT

11th National Cancer Institute – European Organization for Research and Treatment of Cancer – American Association for Cancer Research (NCI-EORTC-AACR) Symposium on New Drugs in Cancer Therapy. Presented November 10, 2000.

MARstem: A novel multilineage hematopoietic stimulant for chemotherapy-induced pancytopenia.

Ronald Blachly, MD1, Spencer McCachren, MD2, Melvin Moore, MD3, Kathleen Rodgers, PhD4,5, Gere DiZerega, MD4,5 , Jamie Oliver, PharmD5

Multilineage pancytopenia occurs following myelosuppressive chemotherapy.  Most hematopoietic stimulants selectively differentiate single cell lines, therefore not preventing chronic progressive pancytopenia. MARstem is a hematopoietic agent that stimulates the proliferation of colony forming units of GEMM, GM, BFU-E, and MEG in cultured bone marrow and human cord blood. This study determined the safety, optimal dose, and proof of concept efficacy of MARstem versus Neupogen following doxorubicin/cyclophosphamide chemotherapy in adjuvant breast cancer. Beginning 2 days after chemotherapy and continuing daily for at least 10 days, fifteen patients received 5 different MARstem doses and 5 patients received Neupogen. Treatment was repeated over 3 cycles of chemotherapy. Additionally, toxicity of each ascending dose was assessed by administering MARstem daily for 7 days followed by a 7-day washout prior to the first cycle of chemotherapy. No dose limiting toxicity was observed following MARstem. The occurrence of adverse events was lower in MARstem than Neupogen patients. No patient required a chemotherapy dose reduction due to a hematologic toxicity. MARstem reduced the frequency of grade 2-4 thrombocytopenia, grade 2-4 anemia, and grade 3-4 lymphopenia compared to Neupogen.  Neupogen patients experienced a lower frequency of grade 3-4 neutropenia compared to MARstem, however, the frequency of grade 3-4 leukopenia was similar in both groups. The most prominent hematologic effect with MARstem was the prevention of thrombocytopenia.

Toxicity

Neupogen

2.5 mcg/kg

10 mcg/kg

50 mcg/kg

75 mcg/kg

100 mcg/kg

Hgb <10gm%

60%

66%

33%

0%

0%

0%

Platelet <80K

60%

0%

0%

0%

0%

0%

Lymph <500

80%

66%

33%

33%

0%

0%

ANC <1000

40%

100%

100%

100%

100%

100%

WBC <2000

60%

66%

66%

66%

100%

33%

Additionally, MARstem reduced the frequency of stomatitis by 30% of that observed with Neupogen treatment. These data suggest that MARstem may be beneficial in preventing or improving pancytopenia following chemotherapy.

1-Northeast Arkansas Clinic, 2-Thompson Cancer Center, 3-Georgia Cancer Center, 4-USC School of Medicine, 5-Maret Pharmaceuticals.