Local modulated electro-hyperthermia in combination with traditional Chinese medicine vs. intraperitoneal chemoinfusion for the treatment of peritoneal carcinomatosis with malignant ascites: A phase II randomized trial

Abstract

The purpose of this study was to develop a safe and non-toxic alternative to the conventional conservative treatment of peritoneal carcinomatosis with malignant ascites (PCMA) by investigating the efficacy and safety of local modulated electro-hyperthermia (mEHT) combined with the traditional Chinese medicine (TCM) 'Shi Pi' herbal decoction, compared with standard intraperitoneal chemoinfusion (IPCI). A randomized, controlled, single-center, open-label clinical trial (phase II) with two parallel groups (allocation ratio, 1:1) was conducted to investigate the efficacy and safety of mEHT+TCM (study group, SG) vs. standard IPCI (control group, CG) in patients with PCMA by intention-to-treat analysis. A total of 260 patients with PCMA were randomly allocated into the two groups (130/130); mEHT was applied for 60 min per session every second day for 4 weeks, for a total of 14 sessions. The TCM decoction was administered orally, at 400 ml daily. In CG, occlusive IPCI with cisplatin (30-60 mg) and fluorouracil (500-600 mg/m2) was applied twice, biweekly. The objective response rate (ORR), quality of life (QoL) and adverse event rate (AER) in the two groups were evaluated 1 month after treatment, analyzed and compared. The present study is registered on ClinicalTrials.gov (NCT02638051). No case was lost or excluded (0/260). The ORR in SG was 77.69% (101/130) vs. 63.85% (73/130) in CG (P<0.05). The QoL in SG was 49.23% vs. 32.3% in CG (P<0.05). The AER in SG was 2.3% (3/130) vs. 12.3% (16/130) in CG (P<0.05). All the adverse events were grade I. In conclusion, the combination of mEHT with TCM achieves better control of PCMA compared with standard IPCI, with less toxicity. Both components of the combination are non-toxic treatments easily tolerated by patients. Thus, this combined treatment may be preferred due to the better benefit-harm balance.

Keywords: malignant ascites; modulated electro-hyperthermia; traditional Chinese medicine.

Figures

Figure 1.

Trial protocol. mEHT, modulated electro-hyperthermia; TCM, traditional Chinese medicine herbal decoction; CDDP, cisplatin; 5FU, 5-fluorouracil; LAB, laboratory investigations. Thin black arrows, mEHT sessions; bold black arrows, IPSI sessions; white arrows, TCM sessions.

Figure 2.

Effect of treatment in terms of objective response rate (ORR) and quality of life (QoL). CR, complete remission; PR, partial remission; NC, no change; PD, progressive disease.

Figure 3.

Comparison of the objective response rate between the present study and the previously published literature. *, randomized trials.

Figure 4.

A typical case of a complete response in a 60-year-old postoperative patient with ovarian cancer (oophorohysterectomy in 2007). The patient was diagnosed with multiple extensive metastases in the liver and the abdominal cavity with ascites in 2013; following administration of four courses of IPCI (CDDP + CTX); the ascites resolved. Abdominal distention and edema of the lower limbs was observed in August, 2014, and one course of IPCI was administered, without relief and with associated with adverse reactions such as nausea, vomiting and loss of appetite. (A and B) The patient was admitted to Clifford Hospital on September 12, 2014, with severe malignant ascites (maximum depth, 10.0 cm) and ultrasound signs of multiple peritoneal carcinomatosis and a KPS of 60%, with significantly compromised hepatic and renal function on blood tests. mEHT with TCM (‘asthenia of both the spleen and kidney’ type) treatment was administered according to the study protocol, without adverse reactions. (C) Following completion of the treatment on October 16, 2014, there was relief of the abdominal distention and the edema of the lower limbs; on blood tests, the hepatic and renal function had returned to normal; the ascites was moderate (5.7 cm deep), with a significant reduction in peritoneal carcinomatosis manifestations; the KPS was 90%. (D) On re-evaluation (November 13, 2014) the hepatic and renal function tests were normal, there was no obvious ascites, no obvious intestinal wall thickening and no characteristic sign of neoplasia; there was also no discomfort and the KPS was 100%. The patient was in complete remission.