in toxicity profile of Gemzar plus carboplatin based on age.
Gender
Gemzar clearance is affected by gender (see CLINICAL PHARMACOLOGY). In the single–agent safety database (N=979 patients), however, there is no evidence that unusual dose adjustments (i.e., other than those already recommended in the DOSAGE AND ADMINISTRATION section) are necessary in women. In general, in single–agent studies of Gemzar, adverse reaction rates were similar in men and women, but women, especially older women, were more likely not to proceed to a subsequent cycle and to experience Grade 3/4 neutropenia and thrombocytopenia.
Pediatric Patients
The effectiveness of Gemzar in pediatric patients has not been demonstrated. Gemzar was eva luated in a Phase 1 trial in pediatric patients with refractory leukemia and determined that the maximum tolerated dose was 10 mg/m2/min for 360 minutes three times weekly followed by a one-week rest period. Gemzar was also eva luated in a Phase 2 trial in patients with relapsed acute lymphoblastic leukemia (22 patients) and acute myelogenous leukemia (10 patients) using 10 mg/m2/min for 360 minutes three times weekly followed by a one week rest period. Toxicities observed included bone marrow suppression, febrile neutropenia, elevation of serum transaminases, nausea, and rash/desquamation, which were similar to those reported in adults. No meaningful clinical activity was observed in this Phase 2 trial.
Patients with Renal or Hepatic Impairment
Gemzar should be used with caution in patients with preexisting renal impairment or hepatic insufficiency as there is insufficient information from clinical studies to allow clear dose recommendation for these patient populations. Administration of Gemzar in patients with concurrent liver metastases or a preexisting medical history of hepatitis, alcoholism, or liver cirrhosis may lead to exacerbation of the underlying hepatic insufficiency.
Drug Interactions
No specific drug interaction studies have been conducted. For information on the pharmacokinetics of Gemzar and cisplatin in combination, see Drug Interactions under CLINICAL PHARMACOLOGY.
Radiation Therapy
A pattern of tissue injury typically associated with radiation toxicity has been reported in association with concurrent and non–concurrent use of Gemzar.
Non–concurrent (given >7 days apart)— Analysis of the data does not indicate enhanced toxicity when Gemzar is administered more than 7 days before or after radiation, other than radiation recall. Data suggest that Gemzar can be started after the acute effects of radiation have resolved or at least one week after radiation.
Concurrent (given together or ≤7 days apart)— Preclinical and clinical studies have shown that Gemzar has radiosensitizing activity. Toxicity associated with this multimodality therapy is dependent on many different factors, including dose of Gemzar, frequency of Gemzar administration, dose of radiation, radiotherapy planning technique, the target tissue, and target volume. In a single trial, where Gemzar at a dose of 1000 mg/m2 was administered concurrently for up to 6 consecutive weeks with therapeutic thoracic radiation to patients with non–small cell lung cancer, significant toxicity in the form of severe, and potentially life–threatening mucositis, especially esophagitis and pneumonitis was observed, particularly in patients receiving large volumes of radiot |
