Quality-adjusted time without symptoms or toxicity analysis of interferon maintenance in multiple myeloma.
OBJECTIVE
In a randomized trial conducted by the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG), interferon alpha-2b (IFN) maintenance therapy (2 mU/m2 subcutaneously three times per week) after successful induction with melphalan and prednisone was found to prolong time to progression in patients with multiple myeloma. A favorable effect on survival was also present, but this difference was of borderline significance. However, IFN toxicity was a concern. To evaluate the trade-off between the clinical benefits of IFN and the associated toxicity, we applied the method of quality-adjusted time without symptoms or toxicity (Q-TWiST).


METHODS
Three clinical health states were defined in this analysis: time with toxicity (TOX), time without disease relapse or toxicity (TWiST), and time following disease relapse (REL). Toxicity information for IFN had been collected using patient-completed diaries so the actual duration of each adverse event could be determined. The health states TOX and REL were weighted using utility scores to account for a possible decrement in quality of life, a weighted sum of the health state durations is used as a measure of quality-adjusted time.


RESULTS
The health state durations were calculated at 72 months median follow-up. Patients in the IFN group gained an average of 9.8 months without disease relapse (P = .001) and 5.8 months of overall survival (P = .074) versus the control group. However, the IFN group suffered an average of 4.1 months of moderate or worse toxicity (P < .001).


CONCLUSIONS
The clinical benefits of IFN outweigh the negative effects associated with treatment toxicity for a wide range of plausible utilities.
Zee
B
B
National Cancer Institute of Canada Clinical Trials Group, Queen's University, Kingston. zeeb@ncic.ctg.queensu.ca
Cole
B
B
Li
T
T
Browman
G
G
James
K
K
Johnston
D
D
Sugano
D
D
Pater
J
J
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006304:Health Status; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008558:Melphalan / Q000008:administration & dosage; D009101:Multiple Myeloma / Q000401:mortality / Q000628:therapy*; D011241:Prednisone / Q000008:administration & dosage; D011788:Quality of Life; D011994:Recombinant Proteins; D012008:Recurrence; D012189:Retrospective Studies; D015996:Survival Rate
D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D008558:Melphalan; D011241:Prednisone