Evaluation of adverse events experienced by older patients participating in studies of molecularly targeted agents alone or in combination.
BACKGROUND
The tolerability of molecularly targeted agents in older patients has not been specifically examined. Adverse event data from clinical trials in the Princess Margaret Hospital Phase II Consortium database were analyzed to address this question.


METHODS
The Consortium database collects trial information on all patients treated with either a molecularly targeted agent alone or in combination since 2001. The frequency of adverse events was determined and analyzed by two different age groups, <65 years and >/=65 years. Toxicity indices (TI) and frequencies of dose-limiting toxicities (DLT), based on adverse events of all causalities (TI(ALL) and DLT(ALL)), and on adverse events that were at least possibly related to the molecularly targeted agent (TI(MTA) and DLT(MTA)), were calculated for both age groups.


RESULTS
Four hundred and one patients who received 1,252 treatment cycles were analyzed from 19 different studies. Baseline performance status was similar between both age groups, but fewer older patients have had multiple prior regimens of chemotherapy or prior radiation therapy. A comparison of the proportions of younger and older patients experiencing DLT(ALL) and DLT(MTA) showed similar results. The TI(MTA) values were comparable between the two age groups in both single agent (3.25 versus 3.00, for <65 versus >/=65 years) and multi-agent (3.65 versus 3.00, for <65 versus >/=65 years) trials.


CONCLUSIONS
Older patients seem to tolerate molecularly targeted therapies either alone or in combination with chemotherapy as well as younger patients. Age alone should not be a barrier in the administration of targeted agents.
Townsley
Carol A
CA
Princess Margaret Hospital Phase II Consortium, Ontario, Canada.
Pond
Gregory R
GR
Oza
Amit M
AM
Hirte
Hal W
HW
Winquist
Eric
E
Goss
Glenwood
G
Degendorfer
Pamela
P
Moore
Malcolm J
MJ
Siu
Lillian L
LL
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D017322:Clinical Trials, Phase II as Topic / Q000706:statistics & numerical data; D019992:Databases as Topic; D016503:Drug Delivery Systems; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D009864:Ontario; D017063:Outcome Assessment, Health Care
D000970:Antineoplastic Agents