plus cisplatin arm, versus 13% on the cisplatin arm. The data suggest cumulative anemia with continued Gemzar plus cisplatin use.
Nausea and vomiting despite the use of antiemetics occurred slightly more often with Gemzar plus cisplatin therapy (78%) than with cisplatin alone (71%). In studies with single–agent Gemzar, a lower incidence of nausea and vomiting (58% to 69%) was reported. Renal function abnormalities, hypomagnesemia, neuromotor, neurocortical, and neurocerebellar toxicity occurred more often with Gemzar plus cisplatin than with cisplatin monotherapy. Neurohearing toxicity was similar on both arms.
Cardiac dysrrhythmias of Grade 3 or greater were reported in 7 (3%) patients treated with Gemzar plus cisplatin compared to one (<1%) Grade 3 dysrrhythmia reported with cisplatin therapy. Hypomagnesemia and hypokalemia were associated with one Grade 4 arrhythmia on the Gemzar plus cisplatin combination arm.
Table 10 presents data from the randomized study of Gemzar plus cisplatin versus etoposide plus cisplatin in 135 patients with NSCLC for the same WHO–graded adverse events as those in Table 8. One death (1.5%) was reported on the Gemzar plus cisplatin arm due to febrile neutropenia associated with renal failure which was possibly treatment–related. No deaths related to treatment occurred on the etoposide plus cisplatin arm. The overall incidence of Grade 4 neutropenia on the Gemzar plus cisplatin arm was less than on the etoposide plus cisplatin arm (28% versus 56%). Sepsis was experienced by 2% of patients on both treatment arms. Grade 3 anemia and Grade 3/4 thrombocytopenia were more common on the Gemzar plus cisplatin arm. RBC transfusions were given to 29% of the patients who received Gemzar plus cisplatin versus 21% of patients who received etoposide plus cisplatin. Platelet transfusions were given to 3% of the patients who received Gemzar plus cisplatin versus 8% of patients who received etoposide plus cisplatin. Grade 3/4 nausea and vomiting were also more common on the Gemzar plus cisplatin arm. On the Gemzar plus cisplatin arm, 7% of participants were hospitalized due to febrile neutropenia compared to 12% on the etoposide plus cisplatin arm. More than twice as many patients had dose reductions or omissions of a scheduled dose of Gemzar as compared to etoposide, which may explain the differences in the incidence of neutropenia and febrile neutropenia between treatment arms. Flu syndrome was reported by 3% of patients on the Gemzar plus cisplatin arm with none reported on the comparator arm. Eight patients (12%) on the Gemzar plus cisplatin arm reported edema compared to one patient (2%) on the etoposide plus cisplatin arm.
Table 9: Selected CTC–Graded Adverse Events From Comparative Trial of Gemzar Plus Cisplatin Versus Single–Agent Cisplatin in NSCLC CTC Grades (% incidence)
Grade based on Common Toxicity Criteria (CTC). Table includes data for adverse events with incidence ≥10% in either arm.
N=217–253; all Gemzar plus cisplatin patients with laboratory or non–laboratory data. Gemzar at 1000 mg/m2 on Days 1, 8, and 15 and cisplatin at 100 mg/m2 on Day 1 every 28 days.
N=213–248; all cisplatin patients with laboratory or non–laboratory data. Cisplatin at 100 mg/m2 on Day 1 every 28 days.
Regardless of causality.
Percent of patients receiving transfusions. Percent transfusions are not CTC–graded events.
Non–laboratory events were graded only if a |
