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CHICAGO, June 5 -- A shorter lead-in time between recommended vitamin B₁₂ supplementation and pemetrexed (Alimta) therapy may reduce treatment delays without impairing its efficacy, researchers said.

In a small study, vitamin B₁₂ injections yielded relatively similar severe and overall treatment-emergent adverse event rates whether administered more or less than seven days before pemetrexed therapy for relapsed non-small cell lung cancer (NSCLC), found Donald A. Richards, M.D., Ph.D., of the Tyler Cancer Center in Tyler, Texas, and colleagues.

Previous trials have shown that pretreatment with folic acid and vitamin B₁₂ reduced overall and severe toxicity from pemetrexed, they noted at the American Society of Clinical Oncology meeting here.

This led to a recommendation that patients receive 350 to 1000 μg of folic acid for at least five days in the week before the first dose of pemetrexed and a 1000 μg injection of vitamin B₁₂ within the same week.

However, "treatment delay to allow vitamin supplementation can be undesirable, particularly with aggressive malignancies," the researchers noted.

In order to see if a shorter vitamin B₁₂ lead-in would alter its benefit, the researchers analyzed data from a phase II trial of pemetrexed given alone at a dose of 500 mg/m² or 900 mg/m² every 21 days for six cycles or until disease progression.

All patients were to receive oral folic acid as recommended and an intramuscular vitamin B₁₂ injection on the first day of the first pemetrexed cycle, or up to 14 days before the first pemetrexed dose.

The analysis included only the 116 participants who received at least one dose of folic acid. Most patients had extensive stage cancer (87.1%) while a minority had limited stage disease (12.9%).

Among them, 86 received vitamin B₁₂ seven or more days before receiving pemetrexed, 18 received it four to six days before treatment, and 12 got it within three days of the first dose.

The researchers found that overall treatment-emergent adverse event rates did not increase as timing of vitamin supplementation got shorter (45.3% for seven or more days before dosing, 33.3% for four to six days, and 50.0% for three or fewer days).

Grade three and four treatment-emergent adverse events showed a similar lack of trend (89.5%, 100.0%, and 83.3%, respectively).

Among the findings for specific adverse events, the researchers reported:

• No clear trend for all grades of hematologic adverse events.
• Similar rates of grade three to four anemia, febrile neutropenia, and thrombocytopenia between groups.
• Neutropenia was more common with shorter lead-in times (16.7% with the three or fewer days time frame, 22.2% for four to six days, and 11.6% for seven or more days).
• Leukopenia was less common with shorter lead-in times (0.0%, 5.6%, and 15.1%, respectively).

Grade three to four nonhematologic adverse events that occurred in at least 5% of patients and were more common with shorter lead-in times included neuropathy, pain, and back pain.

Grade three to four nonhematologic adverse events that occurred in at least 25% of patients and were more common with shorter lead-in times included anorexia (33.3%, 37.8%, and 18.6%, respectively), constipation (25.0%, 22.2%, and 11.6%), and increased cough (25.0%, 16.7%, and 10.5%).

The researchers reported no statistical values for differences between groups, which limits the usefulness of the findings.

Nevertheless, they concluded, "Vitamin B₁₂ given less than seven days before start of pemetrexed treatment does not appear to be associated with increased serious toxicities."

The study was supported by Eli Lilly. The researchers disclosed no conflicts of interest.

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