Forphenicinol enhances the antitumor effects of cyclophosphamide in a model of squamous cell carcinoma.
We examined the interaction between forphenicinol (FPL) and cyclophosphamide (CPA) or ionizing radiation (IR) on the growth of murine squamous cell carcinoma tumors SCCVII. Primary tumors were established in C3H mice by injecting SCCVII tumor cells subcutaneously into the right hind limb. FPL (100 mg/kg for 8 days) and/or CPA (25 mg/kg twice) were administered by intraperitoneal injection. Tumors were irradiated to a total dose of 40 Gy (eight 5-Gy fractions). SCCVII tumor growth was inhibited by FPL (P=0.054), IR (P=0.003) and CPA (P<0.001) compared with control. The combination of FPL and CPA inhibited tumor growth additively compared with either treatment alone in both small- and large-volume tumors. FPL did not significantly enhance the antitumor effects of IR, however, when CPA+FPL were combined with IR, significant tumor growth inhibition was observed compared with FPL alone (P<0.001), CPA alone (P=0.002) and IR alone (P=0.002). Due to its low toxicity profile, FPL may be combined with CPA, IR and other cytotoxic therapies to potentially enhance the therapeutic ratio.
Murphy
Kevin T
KT
Department of Radiation and Cellular Oncology, University of Chicago, 5758 S. Maryland Avenue, MC1105, Chicago, IL 60637, USA.
Wardak
Abdullah
A
Beckett
Michael A
MA
Lopez
Carlos A
CA
Mehta
Neil
N
Kimchi
Eric
E
Salloum
Rabih M
RM
Jaskowiak
Nora T
NT
Posner
Mitchell C
MC
Ohno
Tsuneya
T
Kufe
Donald W
DW
Weichselbaum
Ralph R
RR
Mauceri
Helena J
HJ
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000532:radiotherapy; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D051379:Mice; D008809:Mice, Inbred C3H; D009368:Neoplasm Transplantation; D011878:Radiotherapy; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000276:Adjuvants, Immunologic; D000970:Antineoplastic Agents; C035946:forphenicinol; D003520:Cyclophosphamide; D005998:Glycine