Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murin model of peritoneal carcinomatosis

<p>Abstract</p> <p>Background</p> <p>The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis.</p> <p>Methods</p> <p>Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured <it>in vivo </it>(tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and <it>in vitro </it>(cytotoxicity on human ovarian cancer cells).</p> <p>Results</p> <p><it>In vitro</it>, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. <it>In vivo</it>, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia.</p> <p>Conclusion</p> <p>Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.</p

Intra-operative intra-peritoneal chemotherapy with cisplatin in patients with peritoneal carcinomatosis of ovarian cancer

International audienceBACKGROUND: Intra-peritoneal (i.p.) chemotherapy is an encouraging treatment option for ovarian cancer with peritoneum involvement in addition with intravenous (i.v.) chemotherapy. Intra-operative i.p. chemotherapy is an interesting method of administration by enhancing the diffusion of chemotherapy. This study had assessed the feasibility of intra-operative i.p. chemotherapy in patients with peritoneal carcinoma of ovarian cancer. METHODS: From January 2003 to February 2006, 47 patients with stage III ovarian cancer were treated with standard paclitaxel carboplatin intravenous chemotherapy and debulking surgery with intra-operative i.p. chemotherapy. After optimal cytoreductive surgery, defined by no unresectable residual disease > 1 cm, i.p. chemotherapy was performed during surgery. The peritoneal cavity was filled by 3 litres of isotonic saline pre-heated at 37 degrees and 90 mg of cisplatin. The sequence was repeated twice during 2 hours based on previous published studies which optimized the cisplatin dosage and exposure duration. Optimal diffusion was obtained by stirring by hands during the 2 hours. RESULTS: Median age was 59.6 years. No severe haematological or non-haematological toxicity induced by intra operative i.p. chemotherapy was reported. No patient died due to the complications of surgery or the i.p. chemotherapy. No neurotoxicity occurred, and one patients had renal impairment. CONCLUSION: This study demonstrates the feasibility of intra-operative i.p. chemotherapy with cisplatin after optimal resection of peritoneal tumor nodules. Further randomized trials are planned to investigate the clinical benefit of this therapeutic modality

Efficacy of trabectedin in metastatic solitary fibrous tumor

Solitary fibrous tumor is a rare tumor type and has an unpredictable course. Local recurrence rate varies between 9 and 19%, and rate of metastatic involvement between 0 and 36 %. It is characterized by a typical architecture and immuno-histochemistry tests. The most important prognostic factor is the complete resection of primary tumor. Treatment of recurrences is not clearly established. If a solitary fibrous tumor is too advanced to allow surgical resection, radiotherapy and chemotherapy may be used. The most often used drugs are doxorubicine and\or ifosfamide. We report the case of man with metastatic solitary fibrous tumor treated with trabectedin, administered at a dose of 1.5 mg/m² every 3 weeks. After 3 cycles, metastases had significantly decreased. Recurrence of the disease was demonstrated 8 months after the start of trabectedin. This case shows that trabectedin is a possible treatment option

[Ganglioneuroma revealed by complicated nephritic colic]

International audienceINTRODUCTION: Ganglioneuroma is a rare benign nervous tumour frequently located in the retroperitoneal area. We report the case of a 22-year-old female patient where this tumour was revealed by nephritic colic complicated by pyelitis and kidney abscess. EXEGESIS: The patient presented with brutal feverish lumbar pains and urinary signs. Abundant iconography, in particular contrasted enhanced sonography, allowed to show a massive retroperitoneal lump and a puncture-biopsy indicated a ganglioneuroma which was surgically removed by laparotomy. Signs may be varied and misleading. Biological and radiological exams are useful for the diagnosis which can only be confirmed by the thorough histological examination of the removed sample. CONCLUSION: A large retroperitoneal lump without alteration of the patient's health should point to this diagnosis, since the complete surgical removal leads to recovery without recurrence, but all the other differential diagnoses must first be dismissed

Improvement in intraperitoneal intraoperative cisplatin exposure based on pharmacokinetic analysis in patients with ovarian cancer.

International audienceOvarian cancer is the leading cause of gynecological cancer-related death in Western countries. The present treatment standards for ovarian cancer are based on the association of debulking surgery with platinum-based chemotherapy. Another strategy that could be further investigated is intraperitoneal chemotherapy (IP). We previously described that the 2-h administration of intraoperative IP cisplatin did not reach satisfactory concentrations. In the present study, we present the results of a pharmacokinetic analysis performed after two consecutive 1-h IP 30 mg/l cisplatin administrations. Twenty-seven patients with advanced epithelial cancer classified FIGO stage IIIC were included in the study. Blood and IP samples were taken over a 24-h period, during and after IP treatment. Both total and ultrafiltered (Uf) platinum (Pt) concentration levels were analyzed. Biological and clinical toxicities were also recorded. With this strategy, IP Pt concentrations stayed above the target concentration (10 mg/l) for a satisfactory length of time. The serum Pt concentrations were higher than those observed with the "one-bath" protocol and they induced the occurrence of recoverable renal toxicities (3 grade 1, 7 grade 2 and 4 grade 3). The best predictive parameter for renal failure was the total Pt 24-h Area Under the Curve (AUC) with a threshold value of 25 mg h/l RR = 0.31 (95% CI 0.13 - 0.49, P < 0.01). Administration of an increased amount of cisplatin is feasible and a satisfactory level of IP Pt concentrations is obtained. However, this improvement is associated with an increase in serum Pt levels and resulting renal toxicities. An attractive solution would be to decrease Pt transfer from peritoneum to bloodstream. A phase 1 study using intraoperative IP epinephrine in order to decrease this transfer is presently being carried out

Intraoperative chemotherapy with cisplatin and epinephrine after cytoreductive surgery in patients with recurrent ovarian cancer: a phase I study.

International audienceBACKGROUND: Intraperitoneal (i.p.) epinephrine was shown to increase the accumulation of i.p. cisplatin in tumours, and thus its antitumour effect in a model of peritoneal carcinomatosis in rats. METHODS: To determine the tolerance to i.p. epinephrine with cisplatin, 18 patients with recurrent ovarian carcinoma were intraoperatively treated in this phase 1 study. After maximal cytoreductive surgery, the peritoneal cavity was filled twice for 1 h with 30 mg/l of cisplatin and increasing concentrations of epinephrine (0, 1, 2, 3 mg/l) in 3 l of saline solution at 37 degrees C. RESULTS: No deaths occurred. Three patients were treated at each of the 0, 1 and 2 mg/l epinephrine levels without adverse events. Two of the three patients who received 3 mg/l epinephrine experienced cardiac intolerance. Six additional patients received 2 mg/l of epinephrine without toxicity. A relationship between the serum concentration of epinephrine and occurrence of cardiac toxicity was established. A 60% decrease in serum area under the curve of platinum was calculated in patients receiving i.p. epinephrine compared with i.p. cisplatin alone. Renal toxicity from cisplatin was not increased by epinephrine. No haematological or neurological toxicity was recorded. The other grade 3-4 adverse events [thromboembolism (5), peritonitis (1), abdominal bleeding (1), bowel fistula (1)] occurred as often as usually reported for this heavy surgical procedure. CONCLUSION: The combination of i.p. epinephrine with cisplatin as intraoperative chemotherapy after optimal cytoreductive surgery is feasible. The recommended concentration for further studies is 2 mg/l for i.p. epinephrine

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis in the elderly: A case-controlled, multicenter study

International audienceOBJECTIVE:This study was designed to identify factors associated with morbidity and mortality in patients older than 70 years who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC).BACKGROUND:Major surgery is associated with higher morbidity and mortality in elderly patients. For PC, CRS and HIPEC is the only current potential curative therapy, but the risks inherent to this patient population have called its benefits into question.METHODS:We retrospectively analyzed a multi-center database from 1989 to 2015. All patients who underwent CRS and HIPEC for PC were selected and patients older than 70 years were matched 1:4 with a younger cohort according to cancer origin, peritoneal cancer index (PCI), and completeness of cytoreduction. Major morbidity and mortality were analyzed.RESULTS:Of 2328 patients, 188 patients older than aged 70 years were matched with 704 younger patients. Patients older than aged 70 years demonstrated a higher American Society of Anesthesiologist score (≥ASA III 10.8 vs. 6.6 %, p = 0.008). There was no difference in overall 90-day morbidity (≥70: 45.7 % vs. 7 (95 % CI 1.051-5.798, p = 0.038) and HIPEC duration (95 % CI 1.106-6.235, p = 0.028) were independent factors associated with morbidity in elderly patients.CONCLUSIONS:CRS and HIPEC appear feasible for selected patients older than aged 70 years, albeit with a higher risk of medical complications associated with increased mortality