Bone marrow-sparing and prevention of alopecia by AS101 in non-small-cell lung cancer patients treated with carboplatin and etoposide.
OBJECTIVE
The aim of this study was to evaluate the ability of the immunomodulator AS101 to prevent chemotherapy-induced neutropenia and thrombocytopenia and thus allow patients to receive full-dose antineoplastic agents according to protocol design. We also aimed to determine the production level of various hematopoietic growth factors in treated patients.


METHODS
This study of 44 unresectable or metastatic non-small-cell lung cancer (NSCLC) patients was an open-label prospective randomized study of standard chemotherapy alone versus chemotherapy plus AS101. Each patient received carboplatin (300 mg/m2 intravenously [IV] on day 1 of a 28-day cycle, and etoposide (VP-16) (200 mg/m2 orally) on days 3, 5, and 7 of each cycle. AS101 was administered at 3 mg/m2 three times per week starting 2 weeks before chemotherapy.


RESULTS
AS101, which manifested no major toxicity, significantly reduced neutropenia and thrombocytopenia and thus allowed all treated patients to receive full-dose antineoplastic agents, in contrast to only 28.5% of the control group. Continuous treatment with AS101 significantly reduced the number of days per patient of thrombocytopenia and neutropenia and did not provide protection to tumor cells as reflected by the higher overall response rate compared with the chemotherapy-alone arm. Interestingly, AS101 treatment also significantly prevented chemotherapy-induced alopecia. These effects correlate with the ability of AS101-treated patients to increase significantly the production of colony-stimulating factors (CSFs) interleukin-1 alpha (IL-1 alpha) and IL-6.


CONCLUSIONS
AS101 has significant bone marrow (BM)-sparing effects and prevents hair loss in chemotherapy-treated patients, with minimal overall toxicity. These effects are probably due to increased production of IL-1 alpha, IL-6, and granulocyte-macrophage (GM)-CSF.
Sredni
B
B
Cancer, AIDS and Immunology Research Institute, Marilyn Finkler Cancer Research Center, Bar Ilan University, Ramat Gan, Israel.
Albeck
M
M
Tichler
T
T
Shani
A
A
Shapira
J
J
Bruderman
I
I
Catane
R
R
Kaufman
B
B
Kalechman
Y
Y
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000505:Alopecia / Q000139:chemically induced / Q000517:prevention & control*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000276:immunology; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D005030:Ethylenes / Q000627:therapeutic use*; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control*; D011446:Prospective Studies; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control*
D000276:Adjuvants, Immunologic; D003115:Colony-Stimulating Factors; D005030:Ethylenes; D007375:Interleukin-1; D015850:Interleukin-6; D005047:Etoposide; C054105:ammonium trichloro(dioxoethylene-O,O'-)tellurate; D016190:Carboplatin