Neurotoxicity of cisplatin +/- reduced glutathione in the first-line treatment of advanced ovarian cancer

Abstract

Several drugs have been proposed for chemoprevention from cisplatin (CDDP)‐induced neurotoxicity. For the purpose of this study the effectiveness of reduced glutathione (GSH) during CDDP‐based first‐line treatment was evaluated in a series of 54 patients affected by epithelial ovarian cancer. Neurotoxicity was assessed by clinical examination, vibrametry and neurophysiology before, during and after chemotherapy. First of all, it is noteworthy that GSH cotreatment did not impair CDDP antineoplastic effectiveness. Non‐neurological side effects were similar in the two groups, with the exclusion of oliguria which occured more frequently in CDDP alone‐treated patients. From a neurological point of view, the comparison between CDDP alone and CDDP+GSH treated groups at the end of treatment (CDDP total dose 500–675 mg m−2) constantly evidenced a trend toward less severe neurotoxicity after cotreatment with all methods. Although neuroprotection was not complete, these findings are in agreement with previous preclinical and clinical data and further support the view that chemoprevention with GSH should be considered in CDDP‐treated patients.

Interventions for preventing neuropathy caused by cisplatin and related compounds

“…These trials included participants being treated with; cisplatin for ovarian cancer (27 GSH treated participants and 27 control participants) (Bogliun 1996);cisplatin for ovarian cancer (25 GSH treated participants and 25 control participants) (Cascinu 1995);oxaliplatin for colorectal cancer (26 GSH treated participants and 26 control participants) (Cascinu 2002);oxaliplatin for colorectal cancer (14 GSH treated participants and 13 control participants) (Milla 2009)cisplatin for non-small cell lug cancer (NSCLC) and head and neck cancer (11 GSH treated participants and 9 control participants) (Schmidinger 2000); andCisplatin for ovarian cancer (74 GSH treated participants and 77 control participants) (Smyth 1997). …”

“…Sural SNAP amplitude decreased by a greater amount in control versus GSH arm (58% to 68% in controls versus 12% to 35% in the GSH arm) among participants receiving < 150 mg/m 2 or > 150 mg/m 2 respectively (Bogliun 1996). Similarly, Cascinu et al (Cascinu 1995) documented a significant reduction of sural, median, and ulnar SNAP amplitudes in the control group versus GSH arm.…”

“…Oliguria occurred in 21 of 27 participants in CDDP alone and 10 of 27 participants in the CDDP with GSH group (risk ratio 0.48, 95% CI 0.28 to 0.81) (see Analysis 5.1) (Bogliun 1996). Participants in the GSH group also required less hemotransfusions and showed fewer incidences of thrombocytopenia and anemia than did participants in the control group (Cascinu 1995).…”

Systematic Review: Generating Evidence-Based Guidelines on the Concurrent Use of Dietary Antioxidants and Chemotherapy or Radiotherapy

“…Regarding dose selection, six studies (23%) mentioned the rationale for selecting the GSH dose, with only one study (22) describing the rationale for determining the selected GSH regimen and dose while five studies (33, 38, 40, 43, 46) stated that they followed the dose of previous studies. The other 20 studies (77%) did not mention a justification for choosing their antioxidant dose.…”

The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects

“…In the clinical setting 1500-3000 mg m Ϫ2 GSH is administered i.v. approximately 15 min before chemotherapy (Parnis et al, 1995;Smyth et al, 1997;Bogliun et al, 1996). In contrast with WR-2721, GSH itself produces no toxicity.…”