Author of

• 11692

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  P2.10 - Poster Session 2 - Chemotherapy (ID 207)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Medical Oncology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11695

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    P2.10-003 - A multicenter, proof-of-concept study of short-term supplementation of folic acid and vitamin B₁₂ prior to cisplatin-pemetrexed therapy for non-small cell lung cancer. (ID 186)

    09:30 - 09:30  |  Author(s): T. Shimokawa
    • Abstract

    Background
    Pemetrexed, a multi-targeted antifolate, requires supplementation with folic acid and vitamin B~12~ prior to its first administration in order to reduce toxicity. The lead-in time for this vitamin supplementation is advised to be at least seven days on the drug package insert. Previous studies suggested that parenteral vitamin B~12~ pervades the major organs in 24 hours, while oral folic acid supplementation usually takes much longer than seven days to correct folic acid deficiency. We hypothesized that the lead-in time for vitamin supplementation can be shortened to 24 hours, enabling earlier administration of standard chemotherapy and potential avoidance of treatment alterations due to rapid disease progression before starting chemotherapy. Since only a few retrospective analyses related to early initiation of pemetrexed have been conducted, the first prospective study evaluating shortened vitamin supplementation for pemetrexed-based chemotherapy was planned.

    Methods
    A multicenter, single-arm phase 2 study was conducted. Patients with advanced non-squamous non-small cell lung cancer were enrolled. Major eligibility criteria were adequate organ function, performance status 0-1, no symptomatic brain metastasis, and no prior cytotoxic chemotherapy. Patients who had provided written informed consent were administered 1000 μg of vitamin B~12~ by intramuscular injection and started taking 350-500 μg of folic acid per day. Cisplatin (75 mg/m[2]) plus pemetrexed (500 mg/m[2]) therapy was commenced 24-48 hours after vitamin B~12~ injection and repeated for four cycles unless disease progression or unacceptable toxicity was observed. The primary endpoint was the proportion of patients experiencing neutropenia ≥grade 3. Thirty patients were to be accrued to detect the difference between the expected 30% of patients with neutropenia ≥grade 3 and the null hypothesis of 50%, using a two-stage design with 70% power and 5% alpha. Clinical trial registry number UMIN000006546.

    Results
    From November 2011 to March 2013, 31 patients were enrolled. Their median age was 66 years (range, 34-74 years), with 32% female. Most patients had adenocarcinoma (87%) and stage IV disease (90%). Performance status was 0 in 16 (52%) and 1 in 15 (48%) patients. Of the 30 patients who started chemotherapy within 48 hours from vitamin administration, 21 (70%) patients completed four cycles of cisplatin/pemetrexed therapy. Six (20%) patients discontinued chemotherapy due to disease progression, and the treatment of three (10%) patients was stopped due to adverse events. No treatment-related deaths or grade 4 toxicity occurred. Grade 3 neutropenia was observed in 7% (95%CI, 2-21%) of patients. Other grade 3 toxicities were anemia (two patients), decreased white blood cell count, diarrhea, thromboembolic event, hypertension, and myocardial infarction (one patient, respectively). The plasma homocysteine level before vitamin administration, a marker for vitamin B~12~ and/or folate deficiency, was elevated in four patients, but none of the patients experienced grade 3 toxicities. The response rate and the disease control rate of chemotherapy were 43% (95%CI, 27-61%) and 77% (95%CI, 59-88%), respectively.

    Conclusion
    This study met its primary endpoint. Absence of relationship between baseline homocysteine levels and toxicities of chemotherapy suggests the efficacy of short-term vitamin supplementation. A pragmatic study with a larger cohort that can detect uncommon toxicities is being conducted.