Nine relevant studies were identified, including three RCTs (n=263) and six prospective observational studies (n=117). Two RCTs had a Jadad score of 5 and one a score of 2. Two RCTs were double blind. The Newcastle-Ottawa scores of the observational studies were 4 or 5.
Overall pooled analysis of RCTs and observational studies showed improvements in forced vital capacity and DLCO after 12 months, but only the change in forced vital capacity was statistically significant (WMD 2.83%, 95% CI 0.35 to 5.31). There was evidence for statistical heterogeneity (p<0.00001). Separate analyses by type of study design indicated that there were no statistically significant differences in the RCTs for either outcome and there was evidence of significant statistical heterogeneity. By comparison, the observational studies indicated statistically significant improvements in both forced vital capacity (WMD 4.73%, 95% CI 0.74 to 8.73) and DLCO (WMD 7.48%, 95% CI 3.64 to 11.32), but these data were not presented graphically.
The changes in forced vital capacity and DLCO after 12 months did not differ between oral and intravenous cyclophosphamide administration. Sensitivity analyses did not significantly alter the results.
Limited data of adverse events were reported in the review.