A phase I study of full-dose gemcitabine and regional arterial infusion of nafamostat mesilate for advanced pancreatic cancer.

BACKGROUND: The primary end points of this study were to determine the dose-limiting toxic effects (DLTs), maximum tolerated dose, and a recommended phase II dose of a synthetic serine protease inhibitor, nafamostat mesilate, in combination with full-dose gemcitabine in patients with unresectable locally advanced or metastatic pancreatic cancer. The secondary end point was to assess therapeutic response. PATIENTS AND METHODS: Patients with previously untreated pancreatic cancer received gemcitabine (1 000 mg/m(2) i.v. for 30 min) on days 1, 8, and 15, with nafamostat mesilate (continuous regional arterial infusion for 24 h through a port-catheter system) on days 1, 8, and 15; this regimen was repeated at 28-day intervals. The initial dose of nafamostat mesilate was 2.4 mg/kg and was escalated in increments of 1.2 mg/kg until a dose of 4.8 mg/kg was achieved. A standard '3+3' phase I dose-escalation design was used. Therapeutic response and clinical benefit response were assessed. RESULTS: Twelve patients were enrolled in this study. None of the patients experienced DLTs, and nafamostat mesilate was well tolerated at doses up to 4.8 mg/kg in combination with full-dose gemcitabine. This combination chemotherapy yielded a reduction of a high serum level of the tumor marker CA19-9. Pain was reduced in three of seven patients without oral morphine sulfate. Overall survival was 7.1 months for all patients. CONCLUSION: This phase I study was carried out safely. This combination chemotherapy showed beneficial improvement in health-related quality of life. The recommended phase II dose of nafamostat mesilate in combination with full-dose gemcitabine is 4.8 mg/kg.

Balloon Test Occlusion with Perfusion CT Imaging Utilizing Intraarterial Contrast Injection.

SUMMARY: Balloon Test Occlusion (BTO) is performed to evaluate the collateral flow when a permanent therapeutic occlusion of unilateral carotid artery is planned. BTO with neurological evaluation alone, however, has a rather high false negative rate. In order to improve the sensitivity, several adjunctive procedures such as induced hypotension or cerebral blood flow (CBF) measurement with various modalities have been combined. Perfusion CT (PCT) is another imaging modality that is mainly used for the diagnosis of acute stroke. In this study, we evaluate the efficacy and the safety of BTO combined with PCT in the same procedure utilizing intraarterial contrast injection from the catheter. Seven patients underwent BTO with PCT in our institution. All the procedures were performed in the angio/CT combination suite. BTO was performed in the usual fashion and when the patient passed the 30 minutes' BTO clinically, PCT was performed subsequently. Contrast material was injected from a Pig Tail catheter placed in the ascending aorta. The obtained data were transferred to a workstation and perfusion maps of CBF, cerebral blood volume (CBV), and time to peak (TTP) were generated using software. In three patients, single photon emission CT (SPECT) was also obtained with administering 99 mTc-ethyl cysteinate dimer (99 mTc-ECD) intravenously during BTO. Although all the patients had passed the BTO clinically, the CBF maps of three patients revealed significant decrease in the occluded hemisphere. There was no procedure-related morbidity. PCT using intraarterial contrast injection during BTO was performed successfully and safely. Intraarterial injection allowed us to obtain excellent time-attenuation curves by utilizing less contrast material and less radiation doze.

Deep vein thrombosis during chemotherapy in a patient with advanced testicular cancer: successful percutaneous thrombectomy under temporary placement of retrievable inferior vena cava filter.

A 27-year-old man with advanced testicular cancer experienced two events of deep vein thrombosis (DVT) during three cycles of cisplatin-based combination chemotherapy; the first thrombotic event occurred in the inferior vena cava (IVC) following the initial two cycles of chemotherapy and the second thrombotic event occurred in the right iliac vein following the third cycle. For both thrombotic events, he was successfully managed with thrombolytic therapy and percutaneous thrombectomy using a transcatheter hydraulic thrombectomy device under temporary placement of a retrievable IVC filter. Stasis of the IVC due to compression by a retroperitoneal lymphadenopathy of 7 cm in diameter, which was demonstrated on computed tomographic scans at presentation, was considered a major cause of DVT during chemotherapy. Patients with bulky retroperitoneal disease causing stasis of major veins are at high risk of DVT associated with chemotherapy and thromboprophylaxis should be strongly considered during their chemotherapy.

[Comparative study of the physical properties of microcatheters frequently used for abdominal IVR].

The purpose of this study was to determine the physical properties of commercially available microcatheters through basic experiments. The materials included eleven different types of widely used microcatheters, ten of which were 135 cm in length and the remaining one 113 cm. Five samples of each catheter were examined. For each catheter, we measured the flow rate, flexibility of the tip, rigidity of the proximal part, smoothness of the outer and inner surfaces, kink resistance of the tip, and pressure resistance of the whole catheter. In conclusion, an ideal microcatheter should satisfy the following criteria: 1) the internal lumen must be large enough to allow high flow volume, and the wall must be enforced by braiding to withstand higher injection pressure; 2) the tip of the catheter must be soft, but must increase in hardness as it approaches the proximal end; 3) it must have a hydrophilic coating on the surface for an appropriate length.

Extended intraarterial cisplatin infusion for treatment of gynecologic cancer after alteration of intrapelvic blood flow and implantation of a vascular access device.

PURPOSE: Twenty-two patients with advanced gynecologic cancer underwent extended intraarterial cisplatin infusion after alteration of the intrapelvic blood flow and implantation of a vascular access device (VAD). METHODS: To maximize concentrations of cisplatin at the target lesion, the superior and inferior gluteal arteries were embolized with steel coils. The tip of the catheter was inserted into the internal iliac artery; the opposite end of the catheter was connected to the VAD. RESULTS: Intensive radioisotope accumulation was demonstrated in the anterior division of the pelvis, seen by scintigraphy performed with technetium 99m macroaggregated albumin via the VAD. Local perfusion in the tumor was well seen by ultrasonographic angiography with CO2 microbubbles via the VAD. Continuous consecutive infusion of cisplatin at a rate of 12.5 mg/day via the VAD minimized the toxicity. The overall response rate was 73%. Radical surgery was possible in 16 of the 22 patients after this intraarterial infusion. CONCLUSION: This method was useful for treating advanced gynecologic cancer without significant toxicity.