Recirculant hyperthermic IntraVEsical chemotherapy (HIVEC) in intermediate–high-risk non-muscle-invasive bladder cancer

Abstract

Purpose To examine the effectiveness of hyperthermic intravesical chemotherapy (HIVEC?) with mitomycin-C (MMC) for patients with intermediate–high-risk non-muscle invasive bladder cancer (NMIBC). Materials and methods From November 2010 to April 2015, 40 patients with intermediate–high-risk NMIBC received HIVEC? treatment with a Combat BRS system. Of these patients, 24 received neoadjuvant HIVEC? treatment (eight weekly instillations) before a transurethral resection of the bladder (TURBT) and 16 received adjuvant HIVEC? treatment post-TURBT (four instillations weekly?+?six monthly). The pathological response of each tumour was evaluated after the neoadjuvant treatment. Recurrence rates and adverse effects were evaluated in both groups. Results A total of 40 patients completed the induction therapy: 24 patients received the Neoadjuvant HIVEC? treatment. Of these patients, 15 (62.5%) showed a complete response. Eight patients (33.3%) showed a partial response, and one patient (4.1%) showed no response at all. The 4-year cumulative incidence of recurrence was 20.8%. The adjuvant HIVEC? treatment was given to 16 patients. The 2-year cumulative incidence of recurrence was 12.5% for this group. The incidence and severity of side effects were slightly lower in the adjuvant group than in the neoadjuvant group. However, the difference was not statistically significant (p?<?0.3). Most of the side effects were low grade and had virtually no effect on the treatment plan, and 97% of patients completed all of the HIVEC? instillations scheduled. Conclusions The recirculation of hyperthermic MMC using Combat’s HIVEC? treatment is safe and effective and is capable of achieving good success rates in both neoadjuvant and adjuvant settings. This treatment seems to be appropriate for NMIBC intermediate–high-risk patients who cannot tolerate or have contraindications for standard BCG therapy or in cases in which there are supply issues or shortages of BCG.     

Feasibility of chemohyperthermia with docetaxel‐embedded magnetoliposomes as minimally invasive local treatment for cancer

Hyperthermia is a minimally invasive approach to cancer treatment, but it is difficult to heat only the tumor without damaging surrounding tissue. To solve this problem, we studied the effectiveness of chemohyperthermia with docetaxel‐embedded magnetoliposomes (DMLs) and an applied alternating current (AC) magnetic field. Human MKN45 gastric cancer cells were implanted in the hind limb of Balb‐c/nu/nu mice. Various concentrations of docetaxel‐embedded DMLs were injected into the tumors and exposed to an AC magnetic field (n = 6, each). For comparison with hyperthermia alone, magnetite‐loaded liposome (ML)‐injected tumors were exposed to an AC magnetic field. Furthermore, the results of DML without AC treatment and docetaxel diluted into PBS with AC treatment were also compared (n = 10, each). Tumor surface temperature was maintained between 42 and 43°C. Tumor volume was reduced in the DML group with a docetaxel concentration > 56.8 μg/ml, while a docetaxel concentration > 568.5 μg/ml was required for tumor reduction without hyperthermia. Statistically significant differences in tumor volume and survival rate were observed between the DML group exposed to the magnetic field and the other groups. The tumor disappeared in 3 mice in the DML group exposed to the magnetic field; 2 mice survived over 6 months after treatment, whereas all mice of the other groups died by 15 weeks. Histologically, hyperthermia with DML damaged tumor cells and DML diffused homogeneously. To the best of our knowledge, this is the first report to show that hyperthermia using chemotherapeutic agent‐embedded magnetoliposomes has an anticancer effect.     

Cost-Effectiveness of Intraperitoneal Chemohyperthermia in the Treatment of Peritoneal Carcinomatosis from Colorectal Cancer

Objectives:  Our purpose was to assess the cost-effectiveness of intraperitoneal chemohyperthermia (IPCH) compared to palliative chemotherapy (STANDARD) against peritoneal carcinomatosis arising from colorectal cancer.
Methods:  We performed a retrospective study of 96 patients whose peritoneal carcinomatosis had been diagnosed between January 1998 and December 2003 and treated either with IPCH or with palliative chemotherapy in French comprehensive cancer centers. Patients were followed up over a 3-year period. Effectiveness was measured by restricted mean survival at 3 years. The Bang and Tsiatis method was used to handle cost-censored data. The confidence limits of the mean cost per patient in each group and the mean incremental cost per life-year saved were computed using 1000 bootstrapreplicates. We also computed an acceptability curve for the incremental cost-effectiveness ratio (ICER).
Results:  We found that IPCH improved survival and was more costly than STANDARD treatment. Over a 3-year observation period, IPCH yielded an average survival gain of 8.3 months at the additional cost of €58,086 (95% confidence interval 35,893–112,839) per life-year saved.
Conclusion:  The ICER of IPCH is acceptable given the severity and burden of peritoneal carcinomatosis for which there is no alternative curative treatment.     

胃癌患者术中腹腔内低渗温热灌注化疗的临床研究

目的探讨术中腹腔低渗温热灌注化疗对胃癌患者术后的临床疗效。方法将术中行一次性腹腔温热低渗灌注化疗的49例胃癌患者(治疗组)与未行此方法的47例患者(对照组)的复发及预后情况进行对比。结果手术并发症二组间无显著性差异。治疗组术后复发率(18.37%)显著低于对照组(44.68%),治疗组的复发时间显著晚于对照组,差异有显著性(P<0.05)。治疗组1、35、年生存率分别为87.76%、61.22%和53.06%,而对照组则分别为82.98%、38.30%和31.91%,两组比较3、5年生存率差异有显著性意义(P<0.05)。结论一次性术中腹腔内低渗温热灌注化疗可降低患者术后复发率和提高生存率,并且操作简便安全。     

Efficacy of intraperitoneal chemohyperthermia with oxaliplatin in colorectal peritoneal carcinomatosis. Preliminary results in 24 patients.

BACKGROUND: The complete resection of macroscopic colorectal peritoneal carcinomatosis (PC), followed by intraoperative intraperitoneal chemohyperthermia (IPCH) to treat residual microscopic disease, leads to cure in some patients. We report preliminary results on survival in a phase II study using oxaliplatin (LOHP). PATIENTS AND METHODS: Twenty-four patients with macroscopic colorectal PC underwent complete resection of the PC followed by IPCH with LOHP performed in an open abdominal cavity. The dose of LOHP was 460 mg/m(2) in 2 l/m(2), during 30 min at 43 degrees C, at a flow rate of 2 l/min. During the hour preceding IPCH, they received an intravenous administration of 5-fluorouracil (400 mg/m(2)) and leucovorin (20 mg/m(2)). RESULTS: Mean peritoneal tumoral extension (Sugarbaker's Index) was 16.9 +/- 9.5, median operative duration was 490 min and median blood loss was 965 ml. There were two postoperative deaths (8%) by intracerebral hemorrhage, and morbidity rate was 41.6%. Minimal follow-up was 18 months and median follow-up was 27.4 months (range 18.3-49.6). At 1, 2 and 3 years, overall survival rates were 83%, 74% and 65%, and disease-free survival rates were 70%, 50% and 50%, respectively. Only 32% of the 22 postoperative living patients presented a peritoneal recurrence. A peritoneal index >24 influenced survival, with a 17% recurrence rate at 2 years versus 63% when it was <24 (P = 0.005). CONCLUSION: This new modality of treatment, when feasible, gives encouraging preliminary results, with a promising 3-year survival rate of 65%.     

Peritoneal carcinomatosis of colorectal cancer: incidence,prognosis, and treatment modalities

Background and aims Intraperitoneal carcinomatosis accounts for 25–35% of recurrences of colorectal cancer. Studies demonstrate that peritoneal carcinomatosis is not necessarily a terminal condition with no options for treatment or cure.Results The combination of aggressive cytoreductive surgery and intra-abdominal hyperthermia chemotherapy improves long-term overall survival in selected patients but is a time-consuming procedure (approx. 12 h) and entails high mortality (5%) and morbidity (35%)). Most commonly used drugs are mitomycin C and platinum compounds, which have synergistic toxic effects on tumor cells when hyperthermia is applied.Conclusion Since combined treatment seems promising only in peritoneal carcinomatosis stages I and II, the precondition for a reasonable combined treatment is careful staging. The mode of chemotherapy, the kind of drugs used for chemoperfusion, the timing of surgery, and the role of additional systemic chemotherapy must be evaluated in randomized studies.     

进展期胃癌术前冲击化疗联合术中腹腔内温热化疗疗效观察

目的观察术前短程冲击化疗联合术中即时腹腔内温热灌注化疗治疗进展期胃癌的临床疗效。方法136例进展期胃癌随机分术前短程冲击化疗联合术中腹腔内温热灌注化疗组（治疗1组）、术前短程冲击化疗组（治疗2组）和单纯手术组（对照组）,比较三组患者的手术并发症发生率和术后长期生存率。结果治疗1组的3a生存率为88．1％,明显高于治疗2组（68．1％）和对照组（42．6％）（P〈0．05）,治疗1组2a内无复发,治疗2组、对照组复发率为17．0％、38．3％,差异有统计学意义（P〈0．05）。结论进展期胃癌术前短程冲击化疗联合术中即时腹腔内温热灌注化疗能提高患者生存率,延缓肿瘤复发。     

区域灌注加腹腔低渗热化疗预防胃癌术后复发和转移的临术研究

目的探讨区域灌注加腹腔低渗热化疗对预防胃癌术后复发和转移的价值。方法将136例实行根治术的胃癌患者随机分成两个组。治疗组(68例):术后行区域动脉灌注化疗加腹腔低渗热化疗;对照组(68例):术后行全身静脉化疗,比较两组疗效。结果随访5年,治疗组1、3、5年生存率分别为94.1%(64/68)、77.9%(53/68)、54.4%(37/68);对照组分别为75.0%(51/68)、51.5%(35/68)、29.4%(20/68)。治疗组局部复发率、腹膜转移率、肝转移率和骨髓抑制发生率分别为10.3%(7/68)、19.1%(13/68)、22.1%(15/68)、17.6%(12/68);对照组分别为25.0%(17/68)、45.6%(31/68)、47.1%(32/68)、36.8%(25/68)。两组指标比较,有非常显著性差异(P<0.01)。结论区域动脉灌注化疗结合腹腔低渗热化疗能有效防治胃癌术后局部复发和腹膜转移、肝转移,疗效好于全身静脉化疗,且副作用小。