Efficacy and safety of PI3K/Akt/mTOR inhibitors combined with trastuzumab therapy for HER2-positive breast cancer: a meta-analysis.

OBJECTIVE: Activation of the PI3K/AKT/mTOR pathway in patients with HER2-positive breast cancer is associated with acquired resistance to trastuzumab. This randomized controlled trial (RCTs) meta-analysis was designed to evaluate the clinical efficacy and safety of PI3K/Akt/mTOR inhibitors in combination with trastuzumab in HER2-positive breast cancer. MATERIALS AND METHODS: We searched on Web of Knowledge, PubMed, Embase, Cochrane, CNKI, and ClinicalTrials.Gov for RCTs comparing PI3K/Akt/mTOR inhibitors plus trastuzumab vs. standard trastuzumab treatments. Pooled estimates of progression-free survival (PFS), pathologic complete response (pCR), and incidence of adverse events were determined. RESULTS: 5 studies out of 610 were found to be eligible and were included in our analysis (n=1,548 participants). PI3K/Akt/mTOR inhibitors combination with trastuzumab treatments resulted in a statistically significant increase in PFS compared with conventional trastuzumab therapy (HR 0.82; 95% CI: 0.76-0.90; p<0.00001). The new combination treatment was more effective on hormone receptor-negative patients (HR 0.73; 95% CI: 0.58-0.93; p=0.010). In addition, the combination of PI3K/Akt/mTOR inhibitors with trastuzumab slightly increased the risk of some adverse events, such as neutropenia, leukopenia, fatigue, and anemia. CONCLUSIONS: The combination treatments of PI3K/Akt/mTOR inhibitors and trastuzumab for PI3K/Akt/mTOR inhibitors combined with trastuzumab treatments for patients with HER2-positive breast cancer can improve median progression-free survival while increasing the incidence of adverse events. It is still controversial based on the current evidence. Due to the limited number and quality of included studies, more high-quality studies are needed for further analysis.

Treatment of cancerous ascites and radical gastrectomy with intraperitoneal hyperthermic double-distilled water and cis-diaminodichloro-platinum perfusion.

AIM: To study the therapeutic effect of intraperitoneal hyperthermic double-distilled water and cis-diaminodichloro-platinum (DDP) perfusion for cancerous ascites and radical gastrectomy. METHODS: LACA mice were injected peritoneally with H22 cancer cells (2 × 10(7) tumor cells). Five days later, the mice received treatments with either intraperitoneal perfusion of 37 °C isotonic fluid (group I), or 43 °C simple hyperthermic double-distilled water (group II), isotonic fluid (group III), DDP (group IV) or a combination of the hyperthermic double-distilled water with DDP (group V). A clinical experiment with intraperitoneal hyperthermic double-distilled water perfusion with DDP was carried out from September 1991 through September 1993 with 32 advanced gastric cancer patients who had undergone radical gastrectomy. RESULTS: In comparison with the untreated control group of cancer cell-bearing LACA mice, the mice in all treatment groups showed near complete obliteration of cancer cells in the peritoneal cavity, markedly reduced ascites, prolonged survival times, and reduced growth of peritoneal cancerous nodes. In the clinical experiment, all 32 patients with advanced carcinoma had achieved satisfactory results at the 1-year follow-up, but had unsatisfactory results at the 2-year follow-up. CONCLUSION: The intraperitoneal hyperthermic double-distilled water perfusion with DDP inhibited the occurrence of ascites in LACA mice bearing cancer cells, and prolonged the lifetime of patients with gastric cancer who had undergone radical gastrectomy.