Background: Chemoradiotherapy is the gold standard in therapy of head and neck cancers. In an attempt to reduce the high incidence of treatment associated toxicities a study with intra-arterial chemotherapy via implantable carotid artery catheters was initiated.

Background: Increased dose or dose-dense chemotherapy for platinum-refractory ovarian cancer is limited because of increasing toxicity. In order to break through drug resistance and reduce toxicity, augmented drug exposure was administered only to the abdomen by means of an isolated perfusion system with extracorporeal circuit.

Die Behandlung des malignen Pleuramesothelioms und insbesondere der Stellenwert der chirurgischen Behandlung wird kontrovers diskutiert zumal Radikaloperationen, welche mit deutlicher Morbidität einhergehen, bislang zu keinem klaren Überlebensvorteil geführt haben. Wir berichten über die Ergebnisse einer laufenden Phase II Studie mit regionaler Chemotherapie in Form der isolierten Thoraxperfusion mit Chemofiltration (ITPF).

BACKGROUND Despite various chemotherapeutic drugs and combinations given systemically, the impact of these agents on survival has not been convincing, and drug-related toxicity continues to be the limiting factor. PATIENTS AND METHODS Two hundred and sixty-five patients with locally advanced or metastasizing (UICC III/IV) pancreatic cancer underwent celiac axis infusion with Mitomycin, Mitoxantrone and Cisplatin combined with degradable starch microspheres in 5 courses and 1 course of isolated hypoxic abdominal perfusion and chemofiltration. RESULTS The study end-points were survival and quality of life. Seventy-five percent survival was 6 months, 50% (median) 9 months and 25% was 18 months. Eighty patients survived for one year and more. The longest actual survival time was ten years in a former unresectable stage IV patient. The quality of life improved in responders. No therapy-related hospitalization or increased morbidity was noted. The resectability rate after therapy in long-term survivors (>12 months) was 39%. Peritoneal carcinosis or progression of liver metastases occurred in 18%. The major cause of death in 48% was recurrence at the primary site. CONCLUSION In good responders to arterial infusion and microembolization chemotherapy, the resectability rate increased remarkably. Relapses predominantly occurred at the primary site, and progression of distant metastases and peritoneal lesions may be reduced due to isolated abdominal perfusion.

BACKGROUND/AIMS:Management of patients with heavily pretreated malignant lymphoma failing frontline treatment and salvage high-dose chemotherapy and autologous peripheral stem cell rescue, is problematic. A pilot study was conducted to evaluate isolated thoracic perfusion of drugs by means of stopflow technique.METHODOLOGY:Six patients were enrolled in the study; diagnoses included 4 advanced Hodgkin's disease, 1 primary mediastinal B-cell lymphoma, and 1 anaplastic large cell lymphoma. Patients were aged 18-37 years; 4 presented with bulky mediastinum. They had never achieved a complete response since all had progressed from front-line treatment, and 3 had even failed salvage high-dose chemotherapy with autologous peripheral stem cell rescue. Cisplatin (100 mg/m2) and melphalan (35 mg/m2) were used. Carmustine (100 mg/m2) were added to these 2 drugs and cytarabine (2000 mg/m2) in patients not previously treated by carmustine, etoposide, cytarabine, and melphalan. Epidoxorubicin (70 mg/m2) was added in patients who previously received a suboptimal dosage of antracycline. Drugs were delivered monthly via aortic perfusion performed by means of Aigner's stop-flow technique.RESULTS:Overall 13 cycles of perfusional chemotherapy were administered with a median number of 2 cycles. During the procedures there were no technical, hemodynamic, or vascular complications, and no deaths occurred during surgery. After 1 month, 6 (100%) objective responses after isolated thoracic perfusion were recorded, 3 (50%) of which were complete. Tolerance to therapy was excellent. Hematological toxicity was mild and transfusional support was needed only in one course. At the last follow-up, 2 patients are alive (1 complete response and 1 very good partial response, maintained).CONCLUSIONS:This new therapeutical approach seems very active in recurrent/refractory malignant lymphoma and may play an important role in this setting.

This pilot study was conducted to evaluate the advantage in drug delivery for regional chemotherapy in patients with unresectable recurrent rectal carcinoma by different methods. For this research, the pharmacokinetic advantages of mitomycin C delivery by four different methods were compared: intraaortic infusion with aortic stopflow; intraaortic infusion with inferior vena cava stopflow; intraaortic infusion with aortic and inferior caval vein stopflow (hypoxic pelvic perfusion); and hypoxic pelvic perfusion with hemofiltration. The results of this study indicate that pelvic stopflow infusion followed by hypoxic pelvic perfusion significantly increases mitomycin C concentrations in the blood coming from the tumor site. Also, use of hemofiltration reduces mitomycin C levels in peripheral blood after high‐dose regional chemotherapy. Further investigations involving more patients should be carried out in the future to validate these results.

Intra-arterial infusion includes a variety of treatment modalities, adjusted selectively to chemosensitivity and vascularization. For most drugs, response behaviour of different tumors is concentration dependent and requires improved modes of application of cytotoxics. In the treatment of liver metastases from colorectal cancer and hepatocellular carcinoma, blood flow reduction by micro-embolization with starch microspheres has brought significant advantage in response. Balloon stopflow infusion combined with micro-embolization induced 83% complete remissions in a study including 100 patients with locally recurrent breast cancer. Stepwise increased local exposure demonstrated concentration-dependent response. Stopflow infusion of the celiac axis combined with microspheres for advanced Stage III and IV pancreatic cancer induced a 96% remission rate (n = 24 patients) at a median survival of 10 months. This was confirmed in a series of consecutive studies including 242 patients. Quality of life was significantly improved in all responding patients. Overall pain response was 80%. A prospective randomized trial in this patient group, comparing systemic vs. regional chemotherapy in the form of intra-arterial infusion with tumor adjusted concentrations, was stopped in an early phase because median survival time was significantly prolonged (P = 0.001) in the arterial group.

Fourty-five patients with progressive FIGO IIIc (36/45 pts.) and IV (9/45 pts.) ovarian cancer, who were in progression under prior cisplatin-based chemotherapy, were submitted to aortic infusion and stop flow infusion with the same drugs. 36/45 patients (80%) had four-quadrant and 9/45 patients (20%) had two-quadrant peritoneal carcinosis, 33/45 with severe ascites. Overall clinical response was 93%: 5/45 CR (11%), 21/45 PR (47%), 16/45 MR (35%). Complete resolution of ascites occurred in 9/33 patients (27%), a substantial reduction of ascites of more than 50% in 14/33 patients (43%). Median survival time was 12.5 months, median time to progression 8.6 months. Toxicity was minimal and in most patients performance and quality of life improved shortly after therapy.

Long-term prognosis of gastric cancer patients mainly depends on early diagnosis. Patients submitted to surgery in advanced stages III and IV do not have more than a 10% 5-year survival expectancy [4]. Although gastric cancer has been proved to be chemosensitive [2,3,5,7], and the rationale for adjuvant chemotherapy is therefore well established, there are no sufficient data so far to demonstrate any substantial benefit in survival. To date radical surgery for early gastric cancer remains the only therapeutic modality with a significant cure rate. It has been the objective of this pilot study to find out whether increased local drug concentrations, given via the arterial route through the celiac axis, lead to higher local response rates than systemic chemotherapy, and therefore potentially induce backstaging of the loco-regional tumor burden.

Bei einem 55jährigen Patienten kam es nach einer komplikationslosen Kniegelenksarthroskopie zur Ruptur im Bereich des kaudalen Milzpoles mit Einblutung in das Mesenterium. Durch die unklare klinische Symptomatik war die Diagnose erschwert. Erst das CT erhärtete den Verdacht der Milzruptur. Bei leerer Unfallanamnese und histologisch normalem Organbefund wird eine spontane Ruptur im perioperativen Zeitraum der Kniegelenksarthroskopie diskutiert.

Since systemic application of a high-dose chemotherapy is limited by the extent of intolerable toxicity and overall response rates so far are rather poor, the systemic mode of chemotherapy for metastatic melanoma appears to be of only limited benefit. On the other hand, results from isolated limb perfusion for satellitosis and in-transit metastasis suggest distinct dose-response correlations with tumoricidal properties of appropriate antineoplastic agents. This experience prompted the idea to pilot the anti-tumor action of a high-dose regimen confined to one hemibody compartment for targeted tumor therapy. After having standardized the surgical procedure this goal appeared to be achievable by expanding the perfused area and by simultaneously detoxifying toxic drug levels within the non-perfused compartment by venous filtration. Two initial causal experiences revealed impressive tumor regressions and are therefore reported on preceding subsequent evaluation within a controlled clinical trial being designed at different solid tumors.

Bei 15 Patienten nach Dickdarmresektion wurde eine totale parenterale Ernährung bis zum fünften postoperativen Tag mit einer hochkalorischen streßadaptierten, kohlenhydrat- und aminosäurehaltigen Kombinationslösung durchgeführt. Der Effekt der verwendeten Infu-sionslösung wurde mittels des Blutglukosespiegels, des Gesamteiweißserumspiegels und der Kalium-, Natrium-, Chlorid- und Phosphatserumkonzentrationen im Serum überprüft. Bis zum 5. postoperativen Tag lagen die Bestimmungen im physiologischen Bereich; lediglich der Bl·utzuckerspiegel lag bis ca. 20mg/dl über dem Refe-renzbereich.

In 15 patients after resection of a part of the large intestine the efficacy of a complete solution for total parenteral nutrition was investigated. Glucose concentrations were 20 mg/dl higher than normal from the operation up to the fifth postoperative day. Electrolyte concentrations were normal during the investigation period. There was only a decrease in the total protein concentration to a lower normal range after the operation till the fifth postoperative day. No systemic or special side effects appeared after the infusion.

Since systemic application of a high-dose chemotherapy is limited by the extent of intolerable toxicity and overall response rates so far are rather poor, the systemic mode of chemotherapy for metastatic melanoma appears to be of only limited benefit. On the other hand, results from isolated limb perfusion for satellitosis and in-transit metastasis suggest distinct dose-response correlations with tumoricidal properties of appropriate antineoplastic agents. This experience prompted the idea to pilot the anti-tumor action of a high-dose regimen confined to one hemibody compartment for targeted tumor therapy. After having standardized the surgical procedure this goal appeared to be achievable by expanding the perfused area and by simultaneously detoxifying toxic drug levels within the non-perfused compartment by venous filtration. Two initial causal experiences revealed impressive tumor regressions and are therefore reported on preceding subsequent evaluation within a controlled clinical trial being designed at different solid tumors.