Discussion
nausea, tumor, fatigue, toxicity, toxicities, ill, chills
RECRUITMENT, DISEASE, SOLID TUMORS, TUMOR
To our knowledge, this was the first phase I trial to assess the safety and antitumor activity of intravenous Helixor-M in patients with heavily pretreated advanced solid tumors. We found that the MTD was 600 mg three times a week. The product was found to have an overall manageable safety profile. One patient discontinued treatment within 600 mg, the MTD level, due to treatment-related fatigue. The most common treatment-related AEs were fatigue, nausea, and chills. Grade 3 or 4 treatment-related AEs occurred in 14.8% of patients. Although 5 patients had stable disease and 3 patients experienced tumor reduction receiving a dose within the MTD, there were no objective responses. Serum CEA levels that were positive at baseline stabilized for patients at higher doses, suggesting a dose–response effect. Though statistically nonsignificant, patients’ QoL improved by the end of treatment in total score and in physical, social/family, and functional wellbeing.The safety profile of Helixor-M observed in this study is similar to that of Helixor-P reported in Huber and colleagues (Serum cytokine profiles varied markedly among the subjects due to tumor type differences. Patients with stable disease showed elevated CXCL9 and CXCL10. CXCL9, CXCL10, and CXCL11 share a common receptor, CXCR3, and can mediate the recruitment of cytotoxic T and natural killer cells to solid tumors (Systematic reviews summarized research findings regarding the effects of ME on QoL, chemotherapy toxicity, survival, cancer-related fatigue, and safety. A systematic review suggests that positive effects of ME on QoL and chemotherapy toxicity were found in most RCTs. However, these RCTs had methodologic deficits (e.g., a lack of blinding, high attrition; ref. In conclusion, ME has common toxicities with manageable safety profiles. The MTD is likely dependent upon dose frequency and disease severity. Although no objective responses were recorded in this study, stable disease and tumor shrinkage were observed in some heavily pretreated patients (one to six lines of prior therapy). Moreover, a trend toward stabilization of tumor markers at higher doses was observed, suggesting that higher doses may have led to better responses had less severely ill patients been treated. Finally, ME may improve the QoL of patients with heavily pretreated advanced solid tumors. Improved QoL may enable patients to tolerate therapy longer. Future phase II trials can explore the optimal timing and dose frequency of intravenous mistletoe extracts. Furthermore, interested investigators can combine ME infusions with chemotherapy or targeted therapy and assess the impact of the infusions on treatment time and patient QoL along with functional immune correlates with rigorously designed and conducted RCTs.