Indications: Mesothelioma: Treatment of unresectable malignant pleural mesothelioma (in combination with cisplatin) Nonsmall cell lung cancer (NSCLC), nonsquamous: Treatment of locally advanced or metastatic nonsquamous NSCLC (as initial treatment in combination with cisplatin, as single-agent maintenance treatment after 4 cycles of initial platinum-based double therapy, and single-agent treatment after prior chemotherapy). Limitation of use: Not indicated for the treatment of squamous cell NSCLC.

Cautions: history of cardiovascular disease; diabetes; prophylactic folic acid and vitamin B12 supplementation required, concomitant nephrotoxic drugs including non- steroidal anti-inflammatory drugs.

Contra-indications: Severe hypersensitivity to pemetrexed or any component of the formulation. Canadian labeling (additional contraindications; not in U.S. labeling): Concomitant yellow fever vaccine Obesity: ASCO Guidelines for appropriate chemotherapy dosing in obese adults with cancer:

Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative. manage regimen-related toxicities in the same manner as for nonobese patients.

if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved.

Renal impairment: CrCl ≥45 ml/minute: No dosage adjustment necessary.

CrCl <45 ml/minute: Use is not recommended (an insufficient number of patients have been studied for dosage recommendations).

Concomitant NSAID use with renal dysfunction:

CrCl ≥80 ml/minute: No dosage adjustment necessary. CrCl 45 to 79 ml/minute and NSAIDs with short half-lives (eg, ibuprofen, indometacin, ketoprofen, ketorolac): Avoid NSAID for 2 days before, the day of, and for 2 days following a dose of pemetrexed.

Any creatinine clearance and NSAIDs with long half-lives (eg, nabumetone, naproxen, oxaprozin, piroxicam):

Avoid NSAID for 5 days before, the day of, and 2 days following a dose of pemetrexed.

Hepatic impairment: Grade 3 (5.1 to 20 times ULN) or 4 (>20 times ULN) transaminase elevation during treatment: Reduce pemetrexed dose to 75% of previous dose (and cisplatin).

Side Effects: gastro-intestinal disturbances; oedema; neuropathy; dehydration; conjunctivitis, increased lacrimation; skin disorders; less commonly colitis, arrhythmias, and interstitial pneumonitis; rarely hepatitis; peripheral ischaemia, acute renal failure, Stevens-Johnson syndrome and toxic epidermal necrolysis also reported.

Dose: Adult: Note: Start vitamin supplements 1 week before initial pemetrexed dose Folic acid 400 to 1000 mcg daily orally (begin 7 days prior to treatment initiation; continue daily during treatment and for 21 days after last pemetrexed dose) and vitamin B12 1000 mcg IM 7 days prior to treatment initiation and then every 3 cycles. Give dexamethasone 4 mg orally twice daily for 3 days, beginning the day before treatment to minimize cutaneous reactions. New treatment cycles should not begin unless ANC ≥1500/mm3, platelets ≥100, 000/mm3, and Clcr ≥45 ml/minute.

Malignant pleural mesothelioma (IV): 500 mg/m2 on day 1 of each 21-day cycle (in combination with cisplatin) or (unlabeled) in combination with carboplatin 2006) or (unlabeled) as single-agent therapy.

Nonsmall cell lung cancer, nonsquamous (IV):

Initial treatment: 500 mg/m2 on day 1 of each 21-day cycle (in combination with cisplatin)

Maintenance or second-line treatment: 500 mg/m2 on day 1 of each 21-day cycle (as a single-agent)

Bladder cancer, metastatic (unlabeled use): IV: 500 mg/m2 on day 1 of each 21-day cycle until disease progression or unacceptable toxicity.

Cervical cancer, persistent or recurrent (unlabeled use): IV: 500 mg/m2 on day 1 of each 21-day cycle until disease progression or unacceptable toxicity occurs (Lorusso, 2010) or 900 mg/m2 on day 1 of each 21-day cycle (Miller, 2008)

Ovarian cancer, platinum-resistant (unlabeled use) (IV): 500 mg/m2 on day 1 of each 21-day cycle (Vergote, 2009) Thymic malignancies, metastatic (unlabeled use) (IV): 500 mg/m2 on day 1 of each 21-day cycle for 6 cycles or until disease progression or unacceptable toxicity occurs.