herapy [median treatment volumes 4795 cm3]. Subsequent studies have been reported and suggest that Gemzar administered at lower doses with concurrent radiotherapy has predictable and less severe toxicity. However, the optimum regimen for safe administration of Gemzar with therapeutic doses of radiation has not yet been determined in all tumor types.
ADVERSE REACTIONS
Gemzar has been used in a wide variety of malignancies, both as a single–agent and in combination with other cytotoxic drugs.
Single–Agent Use: Myelosuppression is the principal dose–limiting toxicity with Gemzar therapy. Dosage adjustments for hematologic toxicity are frequently needed and are described in DOSAGE AND ADMINISTRATION.
The data in Table 7 are based on 979 patients receiving Gemzar as a single–agent administered weekly as a 30–minute infusion for treatment of a wide variety of malignancies. The Gemzar starting doses ranged from 800 to 1250 mg/m2. Data are also shown for the subset of patients with pancreatic cancer treated in 5 clinical studies. The frequency of all grades and severe (WHO Grade 3 or 4) adverse events were generally similar in the single–agent safety database of 979 patients and the subset of patients with pancreatic cancer. Adverse reactions reported in the single–agent safety database resulted in discontinuation of Gemzar therapy in about 10% of patients. In the comparative trial in pancreatic cancer, the discontinuation rate for adverse reactions was 14.3% for the Gemzar arm and 4.8% for the 5–FU arm.
All WHO–graded laboratory events are listed in Table 7, regardless of causality. Non–laboratory adverse events listed in Table 7 or discussed below were those reported, regardless of causality, for at least 10% of all patients, except the categories of Extravasation, Allergic, and Cardiovascular and certain specific events under the Renal, Pulmonary, and Infection categories. Table 8 presents the data from the comparative trial of Gemzar and 5–FU in pancreatic cancer for the same adverse events as those in Table 7, regardless of incidence.
Table 7: Selected WHO–Graded Adverse Events in Patients Receiving Single–Agent Gemzar WHO Grades (% incidence)* *
Grade based on criteria from the World Health Organization (WHO).
N=699–974; all patients with laboratory or non–laboratory data.
N=161–241; all pancreatic cancer patients with laboratory or non–laboratory data.
N=979.
Regardless of causality.
Table includes non–laboratory data with incidence for all patients ≥10%. For approximately 60% of the patients, non–laboratory events were graded only if assessed to be possibly drug–related.
All Patients
Pancreatic Cancer
Patients
Discontinuations
(%)
All
Grades
Grade
3
Grade
4
All
Grades
Grade
3
Grade
4
All
Patients
Laboratory¶
Hematologic
Anemia
68
7
1
73
8
2
<1
Leukopenia
62
9
<1
64
8
1
<1
Neutropenia
63
19
6
61
17
7
-
Thrombocytopenia
24
4
1
36
|
