Iressa - Side Effects & Drug Interactions

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Concomitant administration of itraconazole (200 mg QD for 12 days), an inhibitor of CYP3A4, with gefitinib (250 mg single dose) to healthy male volunteers, increased mean gefitinib AUC by 88% (see PRECAUTIONS-Drug Interactions section). Co- administration of high doses of ranitidine with sodium bicarbonate (to maintain the gastric pH above pH 5.0) reduced mean gefitinib AUC by 44% (see PRECAU-TIONS- Drug Interactions section).

International Normalized Ratio (INR) elevations and/ or bleeding events have been reported in some patients taking warfarin while on IRESSA therapy. Patients taking warfarin should be monitored regularly for changes in prothrombin time or INR (see PRECAUTIONS-Drug Interactions and ADVERSE REACTIONS sections).

Clinical Studies

Non- Small Cell Lung Cancer (NSCLC) Ð A multicenter clinical trial in the United States evaluated the tumor response rate of IRESSA 250 and 500 mg/ day in patients with advanced non- small cell lung cancer whose disease had progressed after at least two prior chemotherapy regimens including a platinum drug and docetaxel. IRESSA was taken once daily at approximately the same time each day. Two hundred and sixteen patients received IRESSA, 102 (47%) and 114 (53%) receiving 250 mg and 500 mg daily doses, respectively. Study patient demographics and disease characteristics are summarized in Table 1. Forty-one percent of the patients had received two prior treatment regimens, 33% three prior treatment regimens, and 25% four or more prior treatment regimens.

Effectiveness of IRESSA as third line therapy was determined in the 142 evaluable patients with documented disease progression on platinum and docetaxel therapies or who had had unacceptable toxicity on these agents. Table 1: Demographic and Disease Characteristics IRESSA Dose 250 mg/ day 500 mg/ day Characteristic N= 66 (%) N= 76 (%) Age Group 18-64 years 43 (65) 43 (57) 64-74 years 19 (29) 30 (39) 75 years and above 4 (6) 3 (4) Sex Male 38 (58) 41 (54) Female 28 (42) 35 (46) Race White 61 (92) 68 (89) Black 1 (2) 2 (3) Asian/ Oriental 1 (2) 2 (3) Hispanic 0 (0) 3 (4) Other 3 (5) 1 (1) Smoking History Yes (Previous or current smoker) 45 (68) 62 (82) No (Never smoked) 21 (32) 14 (18) Baseline WHO Performance Status 0 14 (21) 9 (12) 1 36 (55) 53 (70) 2 15 (23) 14 (18) Not Recorded 1 (2) 0 (0) Tumor Histology Squamous 9 (14) 11 (14) Adenocarcinoma 47 (71) 50 (66) Undifferentiated 6 (9) 4 (5) Large Cell 1 (2) 2 (3) Squamous and Adenocarcinoma 3 (5) 7 (9) Not Recorded 0 (0) 2 (3) Current Disease Status Locally Advanced 11 (17) 5 (7) Metastatic 55 (83) 71 (93) Table 2 shows tumor response rates and response duration. The overall response rate for the 250 and 500 mg doses combined was 10.6% (95% CI: 6%, 16.8%).