Tubular dysfunction after peritonectomy and chemohyperthermic treatment with cisplatin. (65/241)

Peritoneal carcinomatosis has always been regarded as a contraindication in traditional cancer surgery treatment; however, good results have been reported by using new combined medical-surgical loco-regional techniques. Peritonectomy and chemohyperthermic perfusion with cisplatinum (CIIP) seem to play a central role in obtaining a better survival rate than with the traditional procedures, even though there is a cisplatinum nephrotoxic effect. The aim of this study was to investigate entity and type of renal injury after CIIP. Forty-two patients (12 males and 30 females) with recurrent or primary peritoneal carcinomatosis who underwent peritonectomy and cytoreductive surgery with hyperthermic intraperitoneal chemotherapy with cisplatin were enrolled. A significant worsening in renal function was observed on the third post-operative day and this condition then persisted for three months. A reduction in estimated-Glomerular Filtration Rate (e-GFR) and an alteration in the albumin:creatinine ratio proved tubular injury. On the third post-operative day after cisplatinum administration, a high toxicity peak was found following platinum free fraction excretion. Proximal tubular injury was confirmed even at the three month analysis. A significant correlation between the total protein reduction rate and the decrease in renal function was established. In relation to that, the platinum free fraction could increase because of a binding protein shortage and the nephrotoxic effect could be enhanced due to platinum accumulation within the post-operative period. This finding suggests that the higher the protein reduction is, the lower the e-GFR determination is at three months.  (+info)

Thoracic stop-flow perfusion in the treatment of refractory malignant pleural mesothelioma: a phase I-II evaluation/trial. (66/241)

Malignant pleural mesothelioma (MPM) is an aggressive treatment-resistant tumor with a median survival from diagnosis of 12 months. Although multimodality protocols that combine aggressive surgery and adjuvant chemotherapy or radiotherapy have shown improved survival in selected cases, the majority of patients with MPM are not suitable for radical surgery due to advanced stage and comorbid medical illness. For these patients combination chemotherapy with Pemetrex and Cisplatin should be considered for first line palliative chemotherapy. The therapeutic options available to patients with MPM resistant or refractory to systemic chemotherapy are very limited. Thoracic "stop-flow" perfusion (TSP) is a semi-invasive loco-regional drug delivery system that, limiting the circulation to the thorax during the anticancer agent's infusion, claims the advantage of reaching high drug concentration at the tumor site while maintaining a low systemic toxicity. The aim of this phase I-II study was to evaluate the toxicity profile and efficacy of two different platinum-based combined regimens--cisplatin plus mitomycin-C (MMC) and cisplatin plus melphalan (L-PAM)--administered using TSP technique in patients with advanced or recurrent MPM who had refractory disease after systemic first line chemotherapy. Patients with histologically proven unresectable stage II-III MPM entered this trial. Between January 1995 and December 2001, 27 patients were enrolled in the study and submitted to TSP using the two different chemotherapy cisplatin based regimens: 12 patients received cisplatin 100 mg/m2 plus MMC 20 mg/m2 (MMC arm) and 15 cisplatin 100 mg/m2 plus L-PAM 50 mg/m2 (L-PAM arm). Objective responses were assessed by CT-scan 30 and 60 days after the end of treatment in all 27 enrolled patients. Two patients (7.4%) achieved a complete response, 2 (7.4%) a partial response and 4 (14.8%) a minor response. The remaining 19 patients (70.3%) showed a stable disease. No patients developed progression of the disease following the first TSP. The overall median time to progression was 8.9 months (range 1-41). The median survival time for all patients from the beginning of regional chemotherapy was 16.6 months, with a 1-year survival rate of 62.9%, a 2-year survival rate of 18.5%, and a 3-year survival rate of 7.4%. Our data show that TSP is a relatively effective second-line treatment in patients with progressive disease after systemic chemotherapy, with a low rate of major complications and treatment-related toxicity.  (+info)

Ten years experience in the treatment of pseudomyxoma peritonei by cytoreduction, peritonectomy and semi-closed hyperthermic antiblastic peritoneal perfusion. (67/241)

BACKGROUND: In the literature good results have been reported for the treatment of Pseudomyxoma peritonei (PMP) by cytoreduction, peritonectomy and hyperthermic antiblastic peritoneal perfusion (H.A.P.P.). Forty-eight patients affected by PMP have been treated with this technique over the past ten years. PATIENTS AND METHODS: Peritoneal perfusion has been performed with the original semiclosed tecnique after complete surgical cytoreduction in 188 patients affected by peritoneal carcinomatosis. In 48 of the cases the patients were affected from PMP. Aggressive surgical cytoreduction was performed with multiple visceral resections and peritonectomies. RESULTS: Seventeen patients (38%) presented major perioperative complications, and in five cases the reoperation of the patient was required. In spite of this high complication rate, there was no perioperative mortality. The results of the Kaplan-Meier 5- and 10-year survival analysis, were 94% and 82%, respectively, with a disease-free survival of 80% at 5 years and 70% at 10 years. Thirty-nine patients (81.2%) had no evidence of disease at follow-up (range 1-120 months). DISCUSSION: Up to date, the most effective treatment for PMP has been aggressive cytoreduction plus H.A.P.P.  (+info)

Liposomal doxorubicin with and without TNFalpha in the perfusional treatment of advanced soft tissue limb sarcoma: preliminary results. (68/241)

BACKGROUND: A combination of doxorubicin and tumor necrosis factor alpha (TNFalpha) has been proven to be very effective in the perfusional treatment of advanced soft tissue limb sarcoma both in terms of tumor necrosis and limb conservative surgery rate. Unfortunately, in some patients a grade IV limb reaction has been recorded. The key solution might be the use of liposomal doxorubicin (Caelyx) because the carrier seems to release the drug preferentially in the tumor rather than in the healthy tissue. PATIENTS AND METHODS: Twenty patients were treated with Caelyx: 14 with Caelyx alone and 6 in combination with a low TNFalpha dose (1 mg). In the first series of 14 patients a dose escalation study was carried out starting from a dose of 10 mg/L of limb volume. Six patients were treated with Caelyx (16 mg) and TNFalpha (1 mg). RESULTS: The maximum tolerated dose (MTD) was 16 mg/L as in two patients treated with 18 mg/L a grade IV limb reaction was observed. Tumor response was satisfactory and conservative surgery was carried out in 13 patients. In 6 patients treated with Caelyx and TNFalpha, only a grade I limb reaction was recorded, thus, confirming that TNFalpha did not increase toxicity, at least at a dose of 1 mg. The Caelyx-TNFalpha combination did increase treatment efficacy. Tumor necrosis > or = 70% was observed in 4 out of 6 patients, one with 100% necrosis (pathological complete response). All the patients underwent conservative surgery. CONCLUSION: The Caelyx-TNFalpha combination was proven to increase the efficacy of Caelyx alone, with a very low toxicity. These preliminary results have to be tested in a larger patient population.  (+info)

Hyperthermic isolation limb perfusion with TNFalpha in the treatment of in-transit melanoma metastasis. (69/241)

BACKGROUND: Hyperthermic isolation limb perfusion (HILP) with tumor necrosis factor alpha (TNFalpha) and IFNgamma was pioneered by Lienard and Lejeune in 1988. The TNFalpha was empirically employed at a dosage of 3-4 mg, that is ten times the systemic maximum tolerated dose (MTD). After eighteen years from its first clinical application, more than 300 patients have been treated. The aim of this study is to clarify two major arguments: the TNFalpha dose and eligibility criteria for patient selection. PATIENTS AND METHODS: A phase I-II study has previously been conducted in 20 patients with in-transit melanoma metastases using a combination of melphalan and TNFalpha at dosages ranging from 0.5 to 3.3 mg. Twenty patients were treated and a complete pathological response of 70% was recorded, with no correlation between tumor response and TNFalpha. The dose of 1 mg of TNFalpha provided the best results regarding efficacy and toxicity. On the basis of this results a large phase II SITILO study was undertaken. Patients with stage IIIA - IIIAB (presence of in transit metastases and/or regional node involvement) were considered eligible; a total of 113 patients were enrolled in the study. The disease was bulky (> 10 nodules or fewer nodules with a diameter > or = 3 cm) in 42.5% of the patients and unresectable in 33%. Forty patients were treated with a TNFalpha dosage > 1 mg and 73 with 1 mg. All the patients were submitted to HILP via axillary and iliac vessels for tumor of upper and lower limb, respectively. TNFalpha was injected in the extracorporal circuit at the pre-established dose, followed after 30 minutes by melphalan (13 and 10 mg/L of limb volume for upper and lower limbs, respectively). RESULTS: A grade 1 and 2 limb toxicity was found in 52.9% and 30.1% of the patients, respectively, 5.5% of patients exhibited a grade 3 and 4, whereas grade 5 limb toxicity was not found. The complete and partial responses were 63% and 24.5%, respectively, with an objective response of 87.5%. We tried to correlate the typed tumor response (CR or not CR) and the TNFalpha dosage < or = 1 mg or > 1 mg, but no statistically significant difference was found between the two groups. The bulky disease was the only prognostic factor able to influence the tumor response. CONCLUSION: Only patients with bulky melanoma disease can benefit from HILP with TNFalpha at a low dose of 1 mg.  (+info)

Hepatic arterial chemotherapy with oxaliplatin, folinic acid and 5-fluorouracil in pre-treated patients with liver metastases from colorectal cancer. (70/241)

BACKGROUND: Hepatic arterial chemotherapy (HAC) is an effective treatment of liver metastases from colorectal cancer (CRC). Phase I and II studies have already shown the feasibility and efficacy of intra-arterial oxaliplatin (OXA). PATIENTS AND METHODS: Twenty-one pre-treated patients with liver metastases who received HAC with OXA/folinic acid (FA)/5-fluorouracil (5-FU) at our Division between March 2000 and November 2003, were clinically examined. Most patients were heavily pre-treated with two or more systemic chemotherapeutic regimes. All patients received a percutaneously implanted catheter into the hepatic artery through femoral or transaxillary access. Treatment was administered every 14 days: OXA 100 mg/m2 as a 12-hour infusion on day 1; FA 100 mg/m2 as a 2-hour infusion on days 2 and 3; 5-FU 2600 mg/m2 as a continuous infusion on days 2 and 3. RESULTS: Grade 3-4 toxicities were: asthenia (2 out of 21), transaminase elevation (2 out of 21) and pain (2 out of 21), nausea and vomiting (1 out of 21), neutropenia (1 out of 21), thrombocytopenia (1 out of 21) and neurotoxicity (1 out of 21). Main dose limiting toxicity was right upper quadrant pain. Response rates were: 5% complete response, 19% partial response, 28% stable disease and 48% progressive disease. Two patients became operable and underwent complete resection of liver disease. The median overall survival was 36.1 months. Two-year and 3-year survival rates were 62% and 52%, respectively. CONCLUSION: This regimen is feasible with low toxicity and with an encouraging overall tumor growth control (52%) in a subset of heavily pre-treated patients. Intra-arterial OXA/FA/5-FU should be considered for the treatment of patients pre-treated with systemic chemotherapies with liver metastases from CRC.  (+info)

120 peritoneal carcinomatoses from colorectal cancer treated with peritonectomy and intra-abdominal chemohyperthermia: a S.I.T.I.L.O. multicentric study. (71/241)

A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.  (+info)

Intra-arterial infusion of 5-fluorouracil, leucovorin, epirubicin and carboplatin (FLEC regimen) in unresectable pancreatic cancer: results of a ten-year experience. (72/241)

The final results of a new regimen given intra-arterially for unresectable pancreatic cancer (UPC) are presented. PATIENTS AND METHODS: From January 1994 to January 2006, 5-fluorouracil 1,000 mg/m2, leucovorin 100 mg/m2, epirubicin 60 mg/m2 and carboplatin 300 mg/m2 were administered every 3 weeks into the celiac axis (CA) angiografically (FLEC regimen) to 211 patients with UPC. RESULTS: Seven hundred and sixty-four cycles were administered. Grade 3-4 hematological toxicity was observed in 24%; ematemesis in 4%; grade 3 gastrointestinal toxicity in 3%; grade 3 alopecia in 15%. One sudden death, a pre-infarction angina and a transitory ischemic attack were observed. No complications related to the angiographic procedure took place, but three tunica intima dissections of the iliac artery occurred; 7.6% of patients with partial responses and 50.7% with stable disease were observed. Two hundred and one patients have died; median overall survival was 9.2 months: 10.5 and 6.6 for stage III and IV, respectively. CONCLUSION: The FLEC regimen given intra-arterially is well-tolerated and effective in patients with UPC.  (+info)