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Phase II study to evaluate the safety and efficacy of intravenous palonosetron (PAL) in primary malignant glioma (MG) patients receiving standard radiotherapy (RT) and concomitant temozolomide (TMZ)

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Abstract

Background

In malignant glioma (MG) patients undergoing radiation therapy (RT) with concomitant temozolomide, chemoradiation-induced nausea and vomiting (cRINV) degrades quality of life (QoL) and reduces treatment adherence, which thereby potentially compromises cancer control.

Methods

We conducted a 6-week phase II single-arm trial of PAL, a second-generation 5-HT3RA antiemetic, for cRINV prevention in MG patients receiving radiation therapy (RT; 54–60 Gy) and concomitant daily temozolomide (TMZ; 75 mg/m2/dX42d). Each week before radiation, patients received single-dose palonosetron (PAL) 0.25 mg IV (total = 6 doses). With safety/tolerability as the primary endpoint, the study was designed to differentiate between toxicity rates of 25 % (unacceptable) and 10 % (acceptable) toxicity rates. Secondary endpoints included the percentage of patients achieving cRINV complete response (CR: no emesis or rescue antiemetic) and QoL. Patients reported adverse effects in Common Toxicity Criteria for Adverse Events diaries; recorded vomiting, nausea, and rescue medication use in diaries (which were used to assess cRINV-CR); and reported QoL 4 days/week using the Modified Functional Living Index-Emesis (M-FLIE) and Osoba nausea and vomiting/retching modules.

Results

We enrolled 38 patients (mean age 59 years, 55 % female, 95 % white, 68 % used oral corticosteroids, 76 % reported low alcohol use). Four patients (10.5 %) experienced unacceptable treatment-related toxicity, defined as any grade 3, 4, or 5 non-hematologic toxicity. M-FLIE and Osoba scores showed no evidence of treatment impact on QoL. Overall, cRINV-CR rates for 6 weeks ranged from 67–79 %.

Conclusion

Single-dose weekly PAL is a safe and tolerable antiemetic for cRINV prevention in MG patients receiving standard RT and concomitant TMZ.

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Author information

Authors and Affiliations

  1. Department of Neurosurgery, Duke University Health System, Durham, NC, 27710, USA

    Mary Lou Affronti, Sarah Woodring & Henry S. Friedman

  2. Duke University School of Nursing, Durham, NC, 27710, USA

    Mary Lou Affronti

  3. The Preston Robert Tisch Brain Tumor Center at Duke, Duke University Medical Center, Room 047 Baker House, South Hospital, Trent Drive, Durham, NC, 27710, USA

    Mary Lou Affronti, Sarah Woodring, Katherine B. Peters, Annick Desjardins & Henry S. Friedman

  4. Department of Radiation Oncology, Duke University Health System, Durham, NC, 27710, USA

    Karen Allen & John Kirkpatrick

  5. Department of Neurology, Duke University Health System, Durham, NC, 27710, USA

    Katherine B. Peters & Annick Desjardins

  6. Department of Biostatistics and Bioinformatics, Duke University Health System, Durham, NC, 27710, USA

    James E. Herndon II, Frances McSherry & Patrick N. Healy

  7. Saint Francis Cancer Center, Hartford, CT, 06105, USA

    James J. Vredenburgh

  8. Department of Medicine, Duke University Health System, Durham, NC, 27710, USA

    Henry S. Friedman

  9. Department of Pediatrics, Duke University Health System, Durham, NC, 27710, USA

    Henry S. Friedman

  10. Department of Pathology, Duke University Health System, Durham, NC, 27710, USA

    Henry S. Friedman

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  1. Mary Lou Affronti
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Corresponding author

Correspondence to Mary Lou Affronti.

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The authors declare that they have no conflict of interest.

Disclosures

Eisai pharmaceutical has supported this investigator initiated IRB approved study.

Appendix

Appendix

Table 8 Analyses of overall cRINV complete response to palonosetron by steroid use at baseline
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Affronti, M.L., Woodring, S., Allen, K. et al. Phase II study to evaluate the safety and efficacy of intravenous palonosetron (PAL) in primary malignant glioma (MG) patients receiving standard radiotherapy (RT) and concomitant temozolomide (TMZ). Support Care Cancer 24, 4365–4375 (2016). https://doi.org/10.1007/s00520-016-3276-1

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