Christiane Gog

Isolated hypoxic perfusion with mitomycin C in patients with advanced pancreatic cancer

AIMS Chemotherapy as a palliative therapy option for patients with advanced pancreatic cancer remains disappointing. Some authors have recently claimed high response rates and a prolongation of median survival after regional chemotherapy. Isolated perfusion may result in the highest drug concentrations within the target tissue without causing systemic side-effects. An established, commercially available system of isolated hypoxic perfusion (IHP) was therefore evaluated in patients with unresectable or recurrent pancreatic cancer. PATIENTS AND METHODS IHP was performed in 17 patients with unresectable pancreatic cancer. Five women and 12 men with a median age of 61 years were treated. A 20-min isolated hypoxic perfusion was performed after 40 mg of mitomycin C (MMC) had been instilled into the running perfusion system over 5 min. Tumour response was evaluated by CT-scan 6 weeks after IHP. RESULTS Twenty perfusions were carried out in 17 patients. Within 10 min of perfusion, the perfusates PO2 decreased to 13% of the baseline value. Five minutes after the infusion of MMC a local concentration of 15.2 mg/litre was observed. Toxicity-related deaths did not occur. Nausea and vomiting (NCI> or =II: 12 episodes) were the most frequently observed toxicities after IHP. In five patients (29%) a deep vein thrombosis occurred. None of the treated patients responded to the regimen used in this trial. The median survival time after IHP was 4.2 months (range 1.3-21). CONCLUSIONS The overall rate of side-effects and complications after IHP was high. In spite of some hopeful reports on this treatment in recent years, IHP did not show any benefit in terms of tumour response or median survival. On the basis of these experiences, this procedure should no longer be used as treatment for patients with unresectable or recurrent pancreatic cancer.

Continuous Arterial 5-Fluorouracil and Folinic Acid Chemotherapy for Colorectal Liver Metastases

Background : A liver resection is only possible for about 20% of all patients suffering from liver metastases from colorectal cancer. Alternatively, intra-arterial chemotherapy is an

Relevance of neoadjuvant and adjuvant treatment for patients with resectable liver metastases of colorectal carcinoma

Abstract Background: Excellent results after resection of colorectal liver metastases are associated with a high rate of recurrence. Influenced by positive results of palliative and adjuvant treatment in advanced cancer, various chemotherapy regimens were evaluated to improve long-term results. Methods: The databases Medline and Cancerlit (1982–1998) gave information about 675 patients who were treated either by means of systemic, intra-arterial, intraportal or intraperitoneal administration before or after liver resection. Results: In general, the feasibility of an adjuvant treatment was tested. Proof has been furnished for the practicability of systemic and arterial therapy and for immunotherapy after liver resection whereas, for peritoneal and portal treatment, further studies are necessary. In a few non-randomised trials, it has been possible to discern a trend towards an improvement due to adjuvant postoperative therapy using historical or matched-pair control groups. Until now, only one of five randomised studies has been published. Six months of postoperative adjuvant intra-arterial treatment using 5-fluorouracil (1000 mg/m2 for 5 days every 28 days) and folinic acid (200 mg/m2 for 5 days every 28 days) was compared with observation only. Neither in the intention-to-treat nor in the as-treated analysis was median survival time (34.5 months versus 40.8 months and 39.7 months versus 44.8 months, respectively) significantly increased. As neoadjuvant treatment was successful in primary non-resectable patients, this approach is now being tested in resectable patients. Conclusion: Despite several theoretical reasons for post- or preoperative treatment in resectable patients, every approach should be tested using of controlled studies.

A Pilot Study on Intensive Weekly 24-Hour Intra-Arterial Infusion with 5-Fluorouracil and Folinic Acid for Colorectal Liver Metastases

Purpose: A pilot study was performed to evaluate the tolerance and efficacy of a hepatic arterial infusion (HAI) of 5-fluorouracil (5-FU) and folinic acid (FA) in patients with unresectable liver metastases from colorectal carcinoma. Patients and Methods: In 11 patients, 135 applications of high-dose HAI of 5-FU/FA were administered. All patients had been intra-arterially pretreated, and 2 of them had received an additional intravenous therapy. The chemotherapy regimen consisted of a weekly HAI of FA 500 mg/m2 over 1 h, immediately followed by HAI of 5-FU over 24 h. Four patients received a 5-FU starting dose of 2,000 mg/m2 and 7 patients of 2,400 mg/m2. One course consisted of 12 weekly applications interrupted by 1 week after 6 applications and 4 weeks after 12 applications. Results: The applied regimen caused only mild side effects. Nausea and vomiting were the most frequently side effects with 36 episodes out of 135 applications (WHO grade ≥3: 2 episodes). Diarrhea was a minor problem occurring with 8 episodes (WHO grade ≥3: 1 episode). There was no evidence of myelosuppression, hand-foot syndrome, neurotoxicity, and biliary sclerosis. A partial remission was observed in 3 patients, and a disease stabilization in 2 patients while the disease progressed in 6 patients under high-dose HAI of 5-FU/FA. Conclusion: The present pilot study demonstrates that the weekly high-dose HAI of 5-FU/FA is well tolerated and associated with very mild toxicity. Because of the encouraging response rate in patients, whose disease progressed under the conventional intra-arterial therapy either with 5-FU/FA or 5-fluorodeoxyuridine, this regimen seems to be an effective second-line treatment and should be evaluated in nonpretreated patients in a phase II study.

Die Stellung der regionalen Langzeitchemotherapie bei Lebermetastasen

Summary. In numerous tumors, metastasis can be limited to the liver. In non-resectable patients, regional treatment modalities, especially arterial cytostatic infusion, are favored in contrast to systemic chemotherapy, whereas intraportal or intraperitoneal application is not successful. Improved results with high response rates have been reported after development of intra-arterial (i.a.) long-term regimens with FUdR in patients with colorectal liver metastases using implantable pumps and ports. However, a survival benefit could only be demonstrated in comparison with a control group only treated symptomatically. Because of several reports on major local toxicity of i. a. FUdR treatment (i.e. chemical hepatitis and biliary sclerosis) several other effective i. a. 5-FU regimens have been developed. A randomized study has demonstrated superiority of i. a. 5-FU versus i. a. FUdR. In comparison with systemic treatment, superiority has only been demonstrated in patients with an intrahepatic tumor burden of < 25 %. Publications about regional treatment of patients with breast, gastric cancer or carcinoid liver metastases are rare. Despite the high response rates reported, the benefit of arterial chemotherapy remains questionable. Overall, local long-term chemotherapy cannot be recommended outside of studies as a primary treatment. However, extensive experience and new drugs support the idea of conducting further regional studies.Zusammenfassung. Eine Metastasierung kann bei zahlreichen Tumoren zunächst auf die Leber beschränkt sein. Bei nichtresektablen Befunden wurden zahlreiche regionale Therapiemodalitäten insbesondere die intraarterielle (i.a.) Chemotherapie vorteilhafter als eine systemische Behandlung angesehen, während nur in Ausnahmen eine portale oder intraperitoneale Therapie erfolgreich war. Nach Weiterentwicklung der arteriellen Langzeittherapie mit Fluorodeoxyuridine (FUdR) und dem Einsatz implantierbarer Pumpen oder Portsysteme konnte bei Lebermetastasen colorectaler Tumoren eine hohe Ansprechrate erreicht werden. Eine Verlängerung der Überlebenszeit konnte aber nur im Vergleich mit einer lediglich symptomatisch behandelten Kontrollgruppe bewiesen werden. Aufgrund einer hohen lokalen Toxizität der i. a. FUdR-Therapie über 14 Tage, wie chemischer Hepatitis und biliärer Sklerose, wurde in Europa eine effektive i. a. folinsäuremodulierte 5-Fluorouracil-Therapie entwickelt. Der randomisierte Vergleich zeigte eine Überlegenheit dieser i. a. 5-FU-Therapie vs. i. a. FUdR. Gegenüber einer systemischen 5-FU/FS-Therapie profitierten jedoch nur Patienten mit einem Tumorvolumen < 25 % in der Subgruppenanalyse. Die Wertigkeit der arteriellen Behandlung bleibt trotz hoher Ansprechraten fraglich. Über eine arterielle Behandlung von Mamma-, Magen- oder Carcinoidlebermetastasen liegen nur wenige Berichte vor. Somit stellt die i. a. Therapie als primäre Option außerhalb von Studien kein Standardverfahren dar. Die zahlreichen Erfahrungen und neue Substanzen ermöglichen aber die Konzeption attraktiver regionaler Studien.

A randomised phase III intergroup trial comparing high-dose infusional 5-fluorouracil with or without folinic acid with standard bolus 5-fluorouracil/folinic acid in the adjuvant treatment of stage III colon cancer: The Pan-European Trial in Adjuvant Colon Cancer 2 study

PURPOSE To investigate whether infusional high-dose 5-flurouracil (HD-FU) provides a significant improvement in recurrence-free survival (RFS) and overall survival (OS) compared with a standard bolus 5-FU regimen (Mayo Clinic) in patients with curatively resectable stage III colon cancer. METHODS Patients (n=1601) were randomised to receive either the Mayo Clinic regimen or one of the three HD-FU regimens; LV5FU2, the Arbeitsgemeinschaft Internistische Onkologie (AIO) or the Grupo Espaňol para el Tratamiento Digestivos (TTD), the data from which were combined to provide the HD-FU arm for final analysis. RESULTS Patients were evenly balanced for age, TMN, tumor grade and vascular and lymphatic invasion. Median follow-up was approximately 42months, RFS (hazard ratio [HR]=0.997) and OS (HR=0.96) (primary end-point) were not statistically different between the two treatment arms. Infusional HD-FU was generally better tolerated than bolus 5-FU regimen. CONCLUSIONS Infusional HD-FU does not improve RFS and OS in curatively resected stage III colon cancer patients compared to the Mayo Clinic regimen, but is less toxic.

Intravenous Weekly High-Dose Infusion of 5-Fluorouracil and Folinic Acid in Pretreated Patients with Metastatic Colorectal Cancer

Background: Effective second-line treatments of inoperable metastatic colorectal cancer are rare. Therefore, the efficacy and toxicity of weekly intravenous high-dose infusions of 5

SOP – Darmpassagestörung in der Palliativmedizin

Onkologe 2017 · 23:566–572 DOI 10.1007/s00761-017-0239-1 Online publiziert: 17. Mai 2017

Erratum zu: SOP – Darmpassagestörung in der Palliativmedizin

com/syringe-driver-database-introduction.html. Zugegriffen:3.Nov.2016 14. Negro S, Reyes R, Azuara ML, Sánchez Y, Barcia E (2006) Morphine, Haloperidol and hyoscine N-butylbromide combined in s. c. infusion solutions: compatibility and stability. Int J Pharm 307(2):278–284 15. Bausewein C, Roller S, Voltz R (2015) Leitfaden Palliative Care, 5. Aufl. Urban & Fischer Elsevier, München 16. Watson M, Lucas C, Hoy A, Back I (2005) Oxford handbook of palliative care, 1. Aufl. Oxford UniversityPress,Oxford 17. Bruera E, MacEachern T, Macmillan K, Miller MJ, Hanson J (1993) Local tolerance to subcutaneous infusionsofhighconcentrationsofhydromorphone: A prospective study. J Pain Symptom Manage 8(4):201–204 18. Bausewein C (2007) Unter welchen Bedingungen istdie subkutaneGabevonFlüssigkeiten indiziert? Internist (Berl)48(4):439–441 19. Herndon C (2001) Continuous subcutaneous infusionpractices of United States hospices. J Pain SymptomManage22(6):1027–1034 20. Mitten T (2001) Subcutaneous drug infusions: a review of problems and solutions. Int J Palliat Nurs7(2):75–85 21. Eisenchals JH et al (2005) Low-dose levomepromazine in refractory emesis in advanced cancer patients: an open-label study. Palliat Med 19(1):71–75 22. Forbat L et al (2017) How and why are subcutaneous fluids administered in an advanced illness population: a systematic review. J Clin Nurs 26(9–10):1204–1216 Onkologe 2017 · 23:664–665 DOI 10.1007/s00761-017-0268-9 Online publiziert: 17. Juli 2017

SOP – Darmpassagestörung in der Palliativmedizin@@@SOP—bowel dysfunction in palliative care medicine

Onkologe 2017 · 23:566–572 DOI 10.1007/s00761-017-0239-1 Online publiziert: 17. Mai 2017