The Mid-Atlantic Oncology Program's comparison of two data collection methods.

The Mid-Atlantic Oncology Program (MAOP) compared clinical trial data collected by circuit riding data managers (CDMs) from the MAOP statistical center with data collected by local data managers (LDMs) from clinics and practices, the latter being the standard data capture method in cancer clinical trials. LDMs and CDMs filled out identical study forms, using the same patient charts, for randomly selected patients on MAOP protocols. All coded answers on the forms were compared by one of the authors (DJ) and discrepant items were resolved in a blinded manner by the local MAOP physician acting as the principal investigator (PI). Thirty-three patient charts were reviewed with 53 pairs of forms completed and 1023 pairs of codes compared. A total of 129 (13%) pairs of codes were considered discrepant. Of the 100 discrepancies resolved (29 items were answered differently by the CDM, LDM, and PI) the PI's answers matched 66 of 100 codes as recorded by the CDMs and 34 of 100 codes as recorded by the LDMs. This results in chi 2 = 9.61 (p less than 0.005), demonstrating a significant difference between the frequency with which the PI's answers matched data collected by the CDMs and LDMs. It was also determined that CDMs consistently coded toxicities as more severe than did LDMs and were more often correct. Given the results of this study, CDMs should be considered an acceptable alternative to LDMs in the context of regional programs.

A critical appraisal of low-dose cytosine arabinoside in patients with acute non-lymphocytic leukemia and myelodysplastic syndromes.

We reviewed 53 publications reporting 751 patients with hematologic malignancies treated with low doses (5 to 20 mg/m2/d) of cytosine arabinoside (LoDAC). Of 507 patients evaluable for response, complete remission (CR) rates varied from 32% for patients with primary acute non-lymphoblastic leukemia (1 degree ANLL) to 16% for patients with hematologic malignancies secondary to previous chemotherapy or following a myelodysplastic syndrome (MDS) (2 degrees ANLL), and 16% for MDS. Median duration of CR was 9.5 months for 1 degree ANLL, and 10.5 months for both 2 degrees ANLL and MDS. Based on limited available survival data, overall median survival for these groups was 9 months, 3 months, and 15 months, respectively. Only three CRs were reported of 31 evaluable patients treated for a variety of other hematologic malignancies. CR rates for patients with 1 degree ANLL greater than or equal to 50 years old was 56%, compared with 29% less than 50 years old (P = .10). While prior chemotherapy was more common in 1 degree ANLL patients less than 50 years of age (86% v 21%; P less than .001), it did not influence response rates in those greater than 50 years of age, suggesting other biases. Hematologic toxicity was mentioned in only 33 of 53 publications, affecting 254 of 289 patients (88%), with at least 15% treatment-related deaths. LoDAC hypothetically acts as a differentiating agent; however, correlative laboratory studies were rarely performed. Cytogenetic data were available for only 15%, and in vitro studies for 10% of all patients with marked discrepancies in the interpretation of results. LoDAC is clearly cytotoxic for both malignant and normal hematopoietic cells. While large numbers of patients have been reported, the lack of well-designed clinical trials prohibits definitive conclusions as to its role as a differentiating agent. Future LoDAC studies should determine optimal dose and schedule, with clinical laboratory correlates to assess differentiation. Trials in ANLL comparing LoDAC with conventional chemotherapy, and in MDS with supportive care alone, may help identify the role of LoDAC. Until appropriate indications can be identified, LoDAC should not be routinely used in clinical practice.