Comparison of the MAID (AI) and CAV/IE regimens with the predictive value of cyclic AMP-responsive element-binding protein 3 like protein 1 (CREB3L1) in palliative chemotherapy for advanced soft-tissue sarcoma patients

Background: Palliative chemotherapy is currently the first-line treatment for advanced soft tissue sarcoma. The purpose of this study was to compare the efficacies of the MAID (AI) and CAV/IE alternating regimens in advanced soft-tissue sarcoma patients. Since resistances to ADM-based chemotherapy and toxicity from doxorubicin are frequently observed in clinical practice, we investigated the association between CREB3L1 expression and survival in advanced soft-tissue sarcomas patients treated with doxorubicin-based palliative chemotherapy. Methods: The cohort under investigation comprised 152 patients who underwent doxorubicin-based first-line palliative chemotherapy for advanced soft-tissue sarcoma at our institution between January 2010 and April 2017. Immunohistochemical analysis and the reverse transcription polymerase chain reaction were used to determine the expression of CREB3L1 in soft-tissue sarcoma specimens prior to first-line palliative chemotherapy. Univariate and multivariate analyses were performed on chemotherapy regimens and CREB3L1 expression levels. The relationship between CREB3L1 expression and survival was also analyzed. Results: The CAV/IE alternating regimen yielded favorable outcomes for response and survival in patients compared with those who received MAID (AI) treatment. The most common toxicity of grades 3 and 4 was leukopenia (58.5 % in the MAID (AI) regimen; 37.1 % in the CAV/IE regimen). The incidence of febrile neutropenia after CAV/IE treatment (7.1 %) was lower than after MAID (AI) treatment (13.4 %). Grade 3 neuralgia was observed in 1.2 % of patients receiving the MAID regimen versus 8.6 % in patients receiving the CAV/IE regimen. High CREB3L1 expression was observed in 48 of 152 patients (31.6 %). Overall survival was significantly higher for CREB3L1 high-expression patients than for CREB3L1 low-expression patients, especially for those also treated with the MAID (AI) regimen. The CREB3L1 expression level was identified as an independent prognostic factor for survival by multivariate analysis. Conclusions: Our study suggests that the CAV/IE alternating regimen may be associated with a better response and more favorable survival than the MAID (AI) regimen in advanced soft-tissue sarcoma patients. Furthermore, the CREB3L1 expression level may predict the efficacy and survival of doxorubicin-based palliative chemotherapy for advanced soft-tissue sarcoma.