Abstract
One hundred and seventeen patients with cerebral glioma (Kernohan grades III and IV) were treated with adjuvant chemotherapy using procarbazine (PCB), CCNU and vincristine (VCR) following whole head irradiation. Cell cultures were prepared from 40 patients in this series and their sensitivity to each cytotoxic drug was assessed in a mictotitration assay with 35 S-methionine incorporation as the end point. Twenty-two of forty (55%) patients responded to PCB and/or CCNU in vitro, and sensitivity to these drugs was linked with increased RFI, whilst sensitivity to VCR was not. The RFI of patients who had responded to PCB or CCNU in vitro was significantly longer than the RFI of patients whose tumours failed to respond in vitro or patients who had not been tested. There was no difference in sex ratio, extent of operation, radiation dose and degree of steroid cover between responders, non-responders and untested groups. Grade III tumours tended to be more sensitive in vitro than grade IV tumours. The age of patients also influenced in vitro chemosensitivity. Patients with chemosensitive tumours in vitro tended to be younger than patients with insensitive tumours in vitro. Further statistical analysis, taking into account these prognostic factors, indicated an association between chemosensitivity in vitro and RFI.
Highlights
Malignant cerebral gliomas represent a formidable clinical challenge despite over 50 years of intensive clinical and experimental investigation
Each patient whose cells were assayed was designated a responder or non-responder to a particular drug on the criteria described in the methods section. 14/40 (35%) of patients responded in vitro to CCNU, 17/40 (42%) of patients responded to PCB and 16/40 (40%) of patients responded to VCR
The length of relapse free interval was compared for those patients who were responders to a particular drug and those who were not
Summary
Biopsy samples were taken at operation for routine diagnostic neuropathological examination. Histology was reported by consultant neuropathologists at The National Hospitals, Queen Square or Maida Vale as either grade III or grade IV malignant glioma. Of 48 biopsies submitted for tissue culture,. Two (4%) became contaminated and 6 (12.5%) cases failed to grow in culture. Ham's F-10 culture medium supplemented with u ml- 1 penicillin, 100 jigml- 1 streptomycin and buffered with 20mM HEPES. Cell culture and the chemosensitivity assay have both been described in detail previously (Thomas et al, 1979; Morgan et al, 1983). Cells at passage level 1 or 2 were diluted to 1-5 x I05cells ml - inoculated onto 96well microtitration plates (1-5 xl cells/well) and incubated at 37°C for 24-72 h. Stock drug solutions were made up as follows: VCR (Oncovin, Eli Lilly) jMgml- 1; PCB (Natulan, Roche) 500 Mg ml - in
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