The efficacy of pemetrexed was evaluated in Study JMCH (NCT00005636), a multicenter, randomized (1:1), single-blind study conducted in patients with MPM who had received no prior chemotherapy. Patients were randomized (n=456) to receive pemetrexed 500 mg/m2 intravenously over 10 minutes followed 30 minutes later by cisplatin 75 mg/m2 intravenously over two hours on Day 1 of each 21-day cycle or to receive cisplatin 75 mg/m2 intravenously over 2 hours on Day 1 of each 21-day cycle; treatment continued until disease progression or intolerable toxicity. The study was modified after randomization and treatment of 117 patients to require that all patients receive folic acid 350 mcg to 1000 mcg daily beginning 1 to 3 weeks prior to the first dose of pemetrexed and continuing until 1 to 3 weeks after the last dose, vitamin B12 1000 mcg intramuscularly 1 to 3 weeks prior to first dose of pemetrexed and every 9 weeks thereafter, and dexamethasone 4 mg orally, twice daily, for 3 days starting the day prior to each pemetrexed dose. Randomization was stratified by multiple baseline variables including KPS, histologic subtype (epithelial, mixed, sarcomatoid, other), and gender. The major efficacy outcome measure was overall survival and additional efficacy outcome measures were time to disease progression, overall response rate, and response duration.
A total of 448 patients received at least one dose of protocol-specified therapy; 226 patients were randomized to and received at least one dose of pemetrexed plus cisplatin, and 222 patients were randomized to and received cisplatin. Among the 226 patients who received cisplatin with pemetrexed, 74% received full supplementation with folic acid and vitamin B12 during study therapy, 14% were never supplemented, and 12% were partially supplemented. Across the study population, the median age was 61 years (range: 20 to 86 years); 81% were male; 92% were White, 5% were Hispanic or Latino, 3.1% were Asian, and <1% were other ethnicities; and 54% had a baseline KPS score of 90–100% and 46% had a KPS score of 70–80%. With regard to tumor characteristics, 46% had Stage IV disease, 31% Stage III, 15% Stage II, and 7% Stage I disease at baseline; the histologic subtype of mesothelioma was epithelial in 68% of patients, mixed in 16%, sarcomatoid in 10% and other histologic subtypes in 6%. The baseline demographics and tumor characteristics of the subgroup of fully supplemented patients was similar to the overall study population.
The efficacy results from Study JMCH are summarized in Table 15 and Figure 8.
|Efficacy Parameter||All Randomized and Treated Patients (N=448)||Fully Supplemented Patients (N=331)|
|Pemetrexed/Cisplatin (N=226)||Cisplatin(N=222)||Pemetrexed/Cisplatin (N=168)||Cisplatin (N=163)|
|Median overall survival(months)||12.1||9.3||13.3||10.0|
|Hazard ratio *||0.77||0.75|
|Log rank p-value||0.020||NA †|
Figure 8: Kaplan-Meier Curves for Overall Survival in Study JMCH
Based upon prospectively defined criteria (modified Southwest Oncology Group methodology) the objective tumor response rate for pemetrexed plus cisplatin was greater than the objective tumor response rate for cisplatin alone. There was also improvement in lung function (forced vital capacity) in the pemetrexed plus cisplatin arm compared to the control arm.
- “OSHA Hazardous Drugs.” OSHA. [https://www.osha.gov/hazardous-drugs]
Pemetrexed Injection is a clear, colorless to pale yellow ready-to-dilute solution in a single-dose vial for intravenous infusion.
NDC 0409-1045-01: Carton containing one (1) single-dose vial, 100 mg/4 mL (25 mg/mL).
NDC 0409-2188-01: Carton containing one (1) single-dose vial, 500 mg/20 mL (25 mg/mL).
NDC 0409-3532-01: Carton containing one (1) single-dose vial, 1 g/40 mL (25 mg/mL).
Storage and Handling
Store Pemetrexed Injection at controlled refrigerated temperature, 2°C to 8°C (36°F to 46°F).
Pemetrexed Injection is a hazardous drug. Follow applicable special handling and disposal procedures. [see References (15)]
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Premedication and Concomitant Medication: Instruct patients to take folic acid as directed and to keep appointments for vitamin B12 injections to reduce the risk of treatment-related toxicity. Instruct patients of the requirement to take corticosteroids to reduce the risks of treatment-related toxicity [see Dosage and Administration (2.4) and Warnings and Precautions (5.1)].
Myelosuppression: Inform patients of the risk of low blood cell counts and instruct them to immediately contact their physician for signs of infection, fever, bleeding, or symptoms of anemia [see Warnings and Precautions (5.1)].
Renal Failure: Inform patients of the risks of renal failure, which may be exacerbated in patients with dehydration arising from severe vomiting or diarrhea. Instruct patients to immediately contact their healthcare provider for a decrease in urine output [see Warnings and Precautions (5.2)].
Bullous and Exfoliative Skin Disorders: Inform patients of the risks of severe and exfoliative skin disorders. Instruct patients to immediately contact their healthcare provider for development of bullous lesions or exfoliation in the skin or mucous membranes [see Warnings and Precautions (5.3)].
Interstitial Pneumonitis: Inform patients of the risks of pneumonitis. Instruct patients to immediately contact their healthcare provider for development of dyspnea or persistent cough [see Warnings and Precautions (5.4)].
Radiation Recall: Inform patients who have received prior radiation of the risks of radiation recall. Instruct patients to immediately contact their healthcare provider for development of inflammation or blisters in an area that was previously irradiated [see Warnings and Precautions (5.5)].
Increased Risk of Toxicity with Ibuprofen in Patients with Renal Impairment: Advise patients with mild to moderate renal impairment of the risks associated with concomitant ibuprofen use and instruct them to avoid use of all ibuprofen containing products for 2 days before, the day of, and 2 days following administration of Pemetrexed Injection [see Dosage and Administration (2.5), Warnings and Precautions (5.6), and Drug Interactions (7)].
Embryo-Fetal Toxicity: Advise females of reproductive potential and males with female partners of reproductive potential of the potential risk to a fetus [see Warnings and Precautions (5.7) and Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with Pemetrexed Injection and for 6 months after the last dose. Advise females to inform their prescriber of a known or suspected pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with Pemetrexed Injection and for 3 months after the last dose [see Warnings and Precautions (5.7) and Use in Specific Populations (8.3)].
Lactation: Advise women not to breastfeed during treatment with Pemetrexed Injection and for 1 week after the last dose [see Use in Specific Populations (8.2)].
This product’s label may have been updated. For current full prescribing information, please visit www.pfizer.com.
Manufactured by: Zydus Hospira Oncology Private Ltd. Ahmedabad 382-213, Gujarat, India.
Distributed by: Hospira, Inc., Lake Forest, IL 60045 USA
|PATIENT INFORMATIONPemetrexed (peh-meh-TREX-ed) Injectionfor intravenous use|
|This Patient Information has been approved by the U.S. Food and Drug Administration.||Issued: 6/2022|
|What is Pemetrexed Injection?|
|Pemetrexed Injection is a prescription medicine used to treat:|
|Do not take Pemetrexed Injection if you have had a severe allergic reaction to any medicine that contains pemetrexed.|
|Before taking Pemetrexed Injection, tell your healthcare provider about all of your medical conditions, including if you: |
|How is Pemetrexed Injection given? |
|What are the possible side effects of Pemetrexed Injection?|
|Pemetrexed Injection can cause serious side effects, including:|
|The most common side effects of Pemetrexed Injection when given alone are:|
|The most common side effects of Pemetrexed Injection when given with cisplatin are:|
|Pemetrexed Injection may cause fertility problems in males. This may affect your ability to father a child. It is not known if these effects are reversible. Talk to your healthcare provider if this is a concern for you.Your healthcare provider will do blood tests to check for side effects during treatment with Pemetrexed Injection. Your healthcare provider may change your dose of Pemetrexed Injection, delay treatment, or stop treatment if you have certain side effects.Tell your healthcare provider if you have any side effect that bothers you or that does not go away.These are not all of the possible side effects of Pemetrexed Injection. For more information, ask your healthcare provider or pharmacist.Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800- FDA-1088.|
|General information about the safe and effective use of Pemetrexed Injection. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or healthcare provider for information about Pemetrexed Injection that is written for health professionals.|
|What are the ingredients in Pemetrexed Injection? Active ingredient: pemetrexedInactive ingredient: monothioglycerol, water for injection and may contain sodium hydroxide for pH adjustment. Manufactured by: Zydus Hospira Oncology Private Ltd.Ahmedabad 382-213, Gujarat, India.|
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