A Phase I Study to Determine the Dose of Methadone as a First Line Agent in the Treatment of Chronic Neuropathic Cancer Pain
A Phase I Study to Determine the Dose of Methadone as a First Line Agent in the Treatment of Chronic Neuropathic Cancer Pain
RATIONALE: Methadone hydrochloride may reduce chronic neuropathic pain in patients with cancer.
PURPOSE: This phase I trial is studying the side effects and best dose of methadone hydrochloride as first-line therapy in treating patients with chronic neuropathic cancer pain.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter study. Patients are assigned to a group according to their average daily dosage of morphine-equivalent for the 3 full days prior to study entry (≤ 45 mg/day OR > 45 but ≤ 75 mg/day).
Patients receive oral methadone hydrochloride at various doses every 8 hours. Patients also may receive breakthrough oral methadone hydrochloride every 2 hours, as needed, for up to 6 breakthrough analgesics per day. Treatment continues for up to 35 days. Treatment stops if the patient has well-controlled pain or experiences intolerable side effects.
Patients complete the Short-Form McGill Pain Questionnaire at baseline. Patients rate their pain according to questions from the Brief Pain Inventory on a scale of 0 (no pain) to 10 (worst pain imaginable) to best describe pain at its worst in the last 24 hours, pain at its least in the last 24 hours, pain on average, and pain right now; record the number and timing of breakthrough analgesic usage, the number of episodes of breakthrough pain, and the total daily dose of methadone hydrochloride; and complete nausea and sleep assessments once daily on days 1-14.
After completion of study treatment, patients are followed at 4, 6-7, and 28 days.
DISEASE CHARACTERISTICS:
Patients diagnosed with cancer and experiencing chronic neuropathic pain syndrome
Pain syndrome diagnosed by the investigator
Pain syndrome related to the effects of cancer or its treatment (i.e., chemotherapy, radiotherapy, and surgery)
Meets 1 of the following criteria:
Experiencing pain for ≥ 4 weeks with an average pain score of ≥ 4 or a worst pain score of ≥ 5 (using the 0-10 Brief Pain Inventory Scale) during the past 24 hours
Requires strong opioids to control pain and is using an oral morphine-equivalent dose of 0-75 mg per day, on average, including breakthrough analgesia, within the past 3 full calendar days
Mixed pain syndrome allowed provided the neuropathic component is the predominant pain
Meets 1 of the following criteria:
PATIENT CHARACTERISTICS:
Karnofsky performance status 40-100%
ALT and AST ≤ 3 times upper limit of normal (ULN)
Creatinine ≤ 2 times ULN
No other known laboratory abnormality that, in the investigator's opinion, would contraindicate study participation
Not pregnant or nursing
Fertile patients must use effective contraception
Mini-Mental State Examination score ≥ 25/30
Able to speak, read, and write in either English or French
Willing to complete study diary and questionnaires
Available for study treatment and follow up (i.e., within reasonable geographical limits of the participating center)
Able to swallow and tolerate oral medications
Patients with prior exposure to methadone hydrochloride must be able to tolerate it
No intractable nausea and vomiting
No presence or history of unstable disease or condition that would, in the investigator's opinion, preclude patient participation in study treatment, such as:
No history of significant alcohol, analgesic, or narcotic substance abuse within the past 6 months
Able physically and mentally to answer questions and comply with study treatment
No patient who lives alone and cannot access at least 1 caregiver who can monitor on a daily basis at home
PRIOR CONCURRENT THERAPY: