Carboplatin Side Effects

ADVERSE REACTIONS To report SUSPECTED ADVERSE REACTIONS Contact Apotex Corp.at 1-800-706-5575 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

For a comparison of toxicities when carboplatin or cisplatin was given in combination with cyclophosphamide, see CLINICAL STUDIES : Use with Cyclophosphamide for Initial Treatment of Ovarian Cancer: Comparative Toxicity.

ADVERSE EXPERIENCES IN PATIENTS WITH OVARIAN CANCER * Use with Cyclophosphamide for Initial Treatment of Ovarian Cancer: Data are based on the experience of 393 patients with ovarian cancer (regardless of baseline status) who received initial combination therapy with carboplatin and cyclophosphamide in two randomized controlled studies conducted by SWOG and NCIC (see CLINICAL STUDIES ).

Combination with cyclophosphamide as well as duration of treatment may be responsible for the differences that can be noted in the adverse experience table.

* * Single Agent Use for the Secondary Treatment of Ovarian Cancer: Data are based on the experience of 553 patients with previously treated ovarian carcinoma (regardless of baseline status) who received single agent carboplatin.

First Line Combination Therapy * Percent Second Line Single Agent Therapy * * Percent Bone Marrow Thrombocytopenia <100,000/mm3 66 62 <50,000/mm3 33 35 Neutropenia <2,000 cells/mm3 96 67 <1,000 cells/mm3 82 21 Leukopenia <4,000 cells/mm3 97 85 <2,000 cells/mm3 71 26 Anemia <11 g/dL 90 90 <8g/dL 14 21 Infections 16 5 Bleeding 8 5 Transfusions 35 44 Gastrointestinal Nausea and vomiting 93 92 Vomiting 83 81 Other GI side effects 46 21 Neurologic Peripheral neuropathies 15 6 Ototoxicity 12 1 Other sensory side effects 5 1 Central neurotoxicity 26 5 Renal Serum creatinine elevations 6 10 Blood urea elevations 17 22 Hepatic Bilirubin elevations 5 5 SGOT elevations 20 19 Alkaline phosphatase elevations 29 37 Electrolytes loss Sodium 10 47 Potassium 16 28 Calcium 16 31 Magnesium 61 43 Other side effects Pain 44 23 Asthenia 41 11 Cardiovascular 19 6 Respiratory 10 6 Allergic 11 2 Genitourinary 10 2 Alopecia 49 2 Mucositis 8 1 In the narrative section that follows, the incidences of adverse events are based on data from 1,893 patients with various types of tumors who received carboplatin as single agent therapy.

Hematologic Toxicity Bone marrow suppression is the dose-limiting toxicity of carboplatin.

Thrombocytopenia with platelet counts below 50,000/mm 3 occurs in 25% of the patients (35% of pretreated ovarian cancer patients);

neutropenia with granulocyte counts below 1,000/mm 3 occurs in 16% of the patients (21% of pretreated ovarian cancer patients);

leukopenia with WBC counts below 2,000/mm 3 occurs in 15% of the patients (26% of pretreated ovarian cancer patients).