Moore, D.H., Donnelly, J., McGuire, W.P., Almadrones, L., Cella, D.F., Herzog, T.J., & Waggoner, S.E. (2003). Limited access trial using amifostine for protection against cisplatin and three hour paclitaxel-induced neurotoxicity: A phase II study of the Gynecologic Oncology Group. Journal of Clinical Oncology, 21(22), 4207–4213.

DOI Link

Study Purpose

To determine the proportion of women who experience significant treatment-induced peripheral neuropathy

Intervention Characteristics/Basic Study Process

Women with gynecologic cancer received combination chemotherapy consisting of cisplatin and paclitaxel via IV 175 mg/m2 over three hours, followed by amifostine 740 mg/m2 and cisplatin 75 mg/m2administered over 90 minutes beginning 15 minutes after amifostine administration.

Sample Characteristics

  • N = 29 enrolled in this limited-access study; 21 completed all six cycles of therapy plus the three-month evaluations
  • FEMALES: 100%
  • KEY DISEASE CHARACTERISTICS: Women with ovarian, primary peritoneal, fallopian tube, endometrial, cervical, or uterine sarcoma
  • OTHER KEY SAMPLE CHARACTERISTICS: Proposed treatment included both cisplatin and paclitaxel chemotherapy.
  • EXCLUSION CRITERIA: Prior chemotherapy or radiation or history of neuropathy

Study Design

  • Phase II study

Measurement Instruments/Methods

  • Measures were done at baseline, before each chemotherapy cycle, and three months after completion of treatment.
  • Chemotherapy-induced peripheral neuropathy (CIPN) was measured using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) toxicity scale, neurotoxicity subscale of the Functional Assessment of Cancer Therapy and Gynecologic Oncology Group, and vibration perception threshold (VPT) testing using the Vibratron II device.

Results

Four of 27 assessable patients experienced dose-limiting toxicity grade 2 or higher CIPN as measured by clinical assessment and NCI CTCAE grading. The number of neuropathic events exceeded the predetermined threshold level for a second stage of accrual and the study was closed.

Amifostine’s level of activity was insufficient to warrant further study in a phase III trial.

Limitations

  • The study contained a relatively small sample size (n = 29) and used a one-group design.
  • Frequent evaluations of CIPN were performed by different professionals, but a detection bias may have been present.
  • Although VPT testing is considered to be the gold standard, it can be inaccurate if the same digits are not used at each assessment.
  • Low inter-observer agreement (46%) was found using the NCI CTCAE.