Cisplatin plus cytosine arabinoside in adults with malignant gliomas

Abstract

A combination of cisplatin and cytosine arabinoside was used to treat 21 patients with glioblastomas and 5 patients with recurrent grade II gliomas. Cisplatin 60-100 mg/m2 was given I.V. in 250 ml 0.45% saline and preceded by 500 ml dextrose 5% in 0.45% saline. Mannitol 50 g was given I.V. concurrently with the cisplatin. Cytosine arabinoside 500-1000 mg/m2 was given by rapid I.V. infusion immediately after the cisplatin. Of 25 evaluable patients, 10 (40%) experienced objective tumor shrinkage on CT scan, and 6 (24%) stabilized. There were 2 complete remissions. Patients who had had no prior treatment had a higher response rate (58%) than those previously treated (23%). Myelosuppression occurred in some patients 2-3 weeks after treatment. Gastrointestinal toxicity (vomiting and diarrhea) was dose-limiting. Two patients had possible neurological toxicity. Recommended doses for further studies are cisplatin 90 mg/m2 and cytosine arabinoside 900 mg/m2.

Complications of chemotherapy in neuro-oncology

“…In the treatment of primary brain tumors, the platinum doses usually used are much lower than those in lung or ovarian cancer, 20 mg/m 2 per cycle instead of 70-100 mg/m 2 per cycle (Stewart et al, 1984;Follezou et al, 1989;Mahaley et al, 1989;Newton et al, 1989;Lord and Coleman, 1991;Kiu et al, 1995;Frenay et al, 2000Frenay et al, , 2005Gilbert et al, 2000;Zustovich et al, 2007). In carboplatin, two chlorine groups are substituted by cyclobutane dicarboxylate, resulting in a lower reactivity with DNA, although the same products are formed.…”

Recapitulation of Tumor Heterogeneity and Molecular Signatures in a 3D Brain Cancer Model with Decreased Sensitivity to Histone Deacetylase Inhibition

“…The proliferation of tumor cells grown in 3D spheroids is typically slower than that of monolayer cultures, exhibits different metabolic profiles and typically displays reduced sensitivity to chemotherapy and radiotherapy [7], [16], [17], [18], [19], [20]. For example, cytosine arabinoside (Ara-C) and Taxol which inhibit proliferation of glioblastoma cell lines in 2D cultures, but have failed clinical trials, show markedly reduced sensitivity in 3D cultures; an Ara-C dose 10 times higher than the effective dose in 2D cultures was necessary to reduce tumor cell proliferation [21], [22], [23]. A more recent 3D spheroid culture system from the Eccles and colleagues has provided automated, quantitative imaging capability that is potentially compatible with high-throughput preclinical targeting studies and may reduce the requirement of animal studies.…”

Cisplatin, ara-C and etoposide (PAE) in the treatment of recurrent childhood brain tumors

“…In vitro synergism has also been demonstrated with ara-C and cisplatin in human colon carcinoma (LoVo) [9] and this combination has shown clinical activity in malignant gliomas [10]. These observations suggest that cisplatin, ara-C and etoposide (PAE) may be an effective combination for pediatric brain tumor treatment.…”