Biomedical subjects

Pierluigi Pilati

Publications and source records attributed to Pierluigi Pilati.

24 records · Page 2Linked to original sources

PubMed2003

Cytoreductive surgery combined with hyperthermic intraperitoneal intraoperative chemotherapy for peritoneal carcinomatosis arising from colon adenocarcinoma.

BACKGROUND: Hyperthermic intraoperative intraperitoneal chemotherapy (HIIC) has been recently proposed to treat peritoneal carcinomatosis arising from colon adenocarcinoma, which is usually regarded as a lethal clinical entity. The purpose of this study was to evaluate the clinical outcome of this combined treatment. METHODS: A retrospective study of 46 patients treated for peritoneal carcinomatosis from colon adenocarcinoma was performed. Thirty-four patients were treated with complete cytoreductive surgery immediately followed by intraoperative HIIC with mitomycin C and cisplatin. The clinical outcome of these 34 patients was analyzed; the median follow-up period was 14.5 months. RESULTS: No postoperative deaths were reported. The postoperative morbidity rate was 35%. No severe locoregional or systemic toxicity was observed. The 2-year overall survival was 31%, and the median survival time and the median time to local disease progression were 18 and 13 months, respectively. Survival and local disease control in patients with well- and moderately differentiated colon adenocarcinoma were significantly better than in those with poorly differentiated tumors. CONCLUSIONS: Considering the dismal prognosis of this condition, HIIC seems to achieve encouraging results in a selected group of patients affected with resectable peritoneal carcinomatosis arising from colon adenocarcinoma. These findings support the conduction of formal phase III randomized trials.

Adenocarcinoma↗

PubMed2002

Hyperthermic intraoperative intraperitoneal chemotherapy with cisplatin and doxorubicin in patients who undergo cytoreductive surgery for peritoneal carcinomatosis and sarcomatosis: phase I study.

BACKGROUND: Hyperthermic intraperitoneal intraoperative chemotherapy (HIIC) combined with cytoreductive surgery (CS) has been proposed as a new multimodal treatment mainly for carcinomatosis of gastrointestinal origin. To evaluate whether this regimen could be used for other tumor types, the authors conducted a Phase I study on HIIC with doxorubicin and cisplatin in patients with peritoneal carcinomatosis or sarcomatosis. PATIENTS AND METHODS: Thirty-one patients with peritoneal carcinomatosis or sarcomatosis (PCS) were enrolled for the study. After completion of CS, HIIC was administered with drug doses that were increased for each consecutive cohort following a three-patient cohort scheme. Thereafter, the accrual was stopped when Grade 4 locoregional or systemic toxicity was observed. The maximum tolerated dose (MTD) was considered the dose in the previous triplet. Drug pharmacokinetics and procedure costs also were analyzed. RESULTS: After CS, residual tumors were not present or measured less than or equal to 3 mm (in dimension) in all cases. Maximum tolerated dose was 15.25 and 43.00 mg L(-1) for doxorubicin and cisplatin, respectively. The perfusate/plasma area under the curve ratios were favorable for both drugs, at 162+/-113 and 20.6+/-6.0, respectively, for doxorubicin and cisplatin. Doxorubicin levels in the peritoneum were higher than in tumor or normal tissue samples. There were no postoperative deaths. Surgery-related complications were observed in 25% of cases. Findings at cost analysis showed that the length of stay in the operation room and intensive care unit were the major cost drivers. CONCLUSIONS: Cytoreductive surgery combined with HIIC is an expensive but feasible therapeutic approach for locally advanced abdominal tumors. Because our preliminary findings for local disease control are encouraging, a Phase II study is now advisable to verify the activity of this promising treatment.

Adult↗

PubMed2002

Isolated limb perfusion in locally advanced cutaneous melanoma.

Isolated limb perfusion (ILP) is a well-established locoregional procedure to deliver high doses of cytostatics to an extremity with multiple in-transit lesions from cutaneous melanoma, with minimal systemic and mild local toxicity. This approach is quite sophisticated and requires accurate monitoring of systemic leakage and of the temperature of the affected limb in order to avoid major systemic and local side effects. Mephalan (L-PAM) is considered the reference drug, although complete responses are reported in only about 50% of patients. Since the early 1990s, tumor necrosis factor-alpha (TNF-alpha) was administered with melphalan in ILP aiming to improve the therapeutic index of this procedure. However, despite the impressive results reported, its role still remains controversial, seemingly confined to large tumor bulk. Fotemustine ILP was proposed as a less toxic alternative to L-PAM, after the results of a pilot experience claiming similar response rates with less local toxicity. A formal phase 1-2 study is now underway to confirm these findings. More straightforward procedures, such as isolated limb infusion, are appealing, as they seem capable of achieving good response rates, are easily repeatable, and are less costly. Larger series are required to validate such results. As potential agents to be delivered through ILP, new vasoactive drugs and agents with new mechanisms of action that interplay with chemotherapy, as well as virus-mediated gene therapy, are being developed.

Antineoplastic Agents↗

PubMedDate not supplied

TNFalpha-based isolated perfusion for limb-threatening soft tissue sarcomas: state of the art and future trends.

The management of limb-threatening soft tissue sarcomas has not yet been standardized. Although local disease control does not affect overall survival, amputation or highly mutilating surgery may be required, which impairs the patient's quality of life. Various neoadjuvant approaches have been proposed to allow limb-sparing surgery for these locally advanced tumors. With TNFalpha-based hyperthermic isolated limb perfusion, the majority of patients can be spared amputation, with acceptable rates of locoregional and systemic complications. As yet, no other available treatment seems to give comparable results when applied to limb-threatening soft tissue sarcomas. Nevertheless, several issues remain to be addressed, such as the type and dose of drugs, repeatability of the procedure, association with radiotherapy, further indications, and evaluation of response. The authors describe the principles underlying TNFalpha-based hyperthermic isolated limb perfusion, review the worldwide experience so far published, and discuss the above issues. The potential future developments of this locoregional therapeutic approach will also be reported.

Chemotherapy, Cancer, Regional Perfusion↗

PubMedDate not supplied

Hyperthermic intraperitoneal intraoperative chemotherapy for peritoneal carcinomatosis arising from gastric adenocarcinoma.

BACKGROUND: Patients with peritoneal carcinomatosis from gastric carcinoma have a dismal prognosis. Hyperthermic intraperitoneal intraoperative chemotherapy (HIIC) has been proposed to treat residual disease after cytoreductive surgery. PATIENTS AND METHODS: From January 1998 through July 2002, 13 patients with peritoneal carcinomatosis from gastric cancer underwent complete cytoreductive surgery followed by HIIC. Chemo-hyperthermia was performed using mitomicin C (3.3 mg/m2) and cisplatin (25 mg m2) for 90 minutes, at a mean intraperitoneal temperature of 41.7 degrees C. RESULTS: No postoperative death was observed. Moderate locoregional toxicity (ileus) was observed in eight cases (42%), while two patients (10%) experienced mild systemic toxicity (myelosuppression or fever). Postoperative complication rate was 26% (pleural effusion, n = 4; septicemia = 1). Median overall survival was 15 months, and the median local progression free survival was 10 months. CONCLUSIONS: Cytoreductive surgery followed by HIIC resulted a feasible procedure, the overall morbidity rate being acceptable. Although the study was conducted in a subset of patients with peritoneal carcinomatosis from gastric cancer (resectable disease), survival results are encouraging.

Adenocarcinoma↗

PubMedDate not supplied

Hepatic metastases of colorectal cancer: locoregional intra-arterial treatment.

A radical resection alone of colorectal hepatic metastases is possible in only 10-20% of the patients but, when resection and ablation are combined, the rate of radicalism can improve. A regional hepatic intra-arterial chemotherapy infusion (HAI) has been introduced in the clinical practice, as a possible alternative approach to systemic chemotherapy. Nevertheless, the introduction of new systemic therapies with monoclonal antibodies, combined to irinotecan or oxaliplatin, recently improved response rates and overall survival ia these patients. Aiming to evaluate a possible influence of HAI in these new treatments, the most important studies underlining the evolution of intrahepatic administration in recent years are reviewed.

Antineoplastic Combined Chemotherapy Protocols↗