Octreotide Alone or in Combination with Rofecoxib as Palliative Treatment for Advanced Hepatocellular Cancer

 

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Zusammenfassung

Einleitung: Das mediane Überleben für fortgeschrittene hepatozelluläre Karzinome (HCC) beträgt ca. 3 Monate. Frühere Octreotid-basierte Therapiestudien ergaben widersprüchliche Aussagen. Material und Methoden: Primäre Zielparameter der offenen, unverblindeten Studie waren das Gesamtüberleben und die Lebensqualität. Patienten wurden prospektiv auf 2 Therapiearme randomisiert, über mindestens 6 Monate oder bis zum Erreichen des klinischen Endpunkts (Tod) behandelt; entweder mittels Octreotidmonotherapie (30 mg im pro Monat, n = 39) oder Kombinationstherapie mit Rofecoxib (zusätzlich bis zu 50 mg/d bid, n = 32). Ergebnisse: Medianes Gesamtüberleben (154 Tage) und mediane Zeit bis zum Tumorprogress (94 Tage) lagen im Erwartungsbereich früherer publizierter Daten zu Octreotide bei HCC. Die beiden Behandlungsgruppen unterschieden sich nicht signifikant (149 vs. 155 Tage, p = 0,849) hinsichtlich Gesamtüberleben. 16/71 behandelten Patienten wiesen entweder eine partielle Remission (n = 3) oder eine stabile Erkrankung bei der Evaluierung nach 3 Monaten auf. Eine Verlangsamung der Tumorprogression ging einher mit einem besseren Überleben (p < 0,0001) bzw. längerem Überleben mit verbesserter Lebensqualität (p < 0,05). Ein CLIP-Score von < 3, eine Pfortaderinfiltration, die Tumorhistologie, Prothrombinzeit, alkalische Phosphatase, Bilirubin, Ferritin und Gamma-Glutamyltransferase waren Faktoren, welche mit dem Überleben assoziiert waren (je p < 0,01). Diskussion: Rofecoxib kombiniert mit Octreotide war bezüglich Gesamtüberlebens nicht wirksamer als Octreotide allein. Octreotide als Therapieoption bei HCC kann generell nicht empfohlen werden, obwohl einzelne Patienten stabile Verläufe zeigten und es ein vergleichsweise günstiges Spektrum an unerwünschten Arzneimittelwirkungen aufweist.

Abstract

Background: Median survival for advanced hepatocellular carcinoma (HCC) is around 3 months. Previous octreotide-based treatment studies revealed conflicting results. Aims and Methods: To determine whether palliative treatment for HCC is beneficial in terms of survival and quality of life (primary outcome measures). Patients were prospectively randomised to receive open-label octreotide 30 mg monthly alone (n = 39) or in combination with rofecoxib (up to 50 mg bid daily, n = 32) for a minimum of six months, or until death occurred. Results: Median overall survival (154 days) and time to progression (94 days) were similar for both treatments and within the range of published trials for octreotide, while adding rofecoxib to octreotide did not alter overall survival (149 vs. 155 days, p = 0.849). Treatment-associated clinical benefit was seen in 16/71 patients (3 patients with partial remissions and 13 with stable disease). Delay in tumor progression was associated with prolonged median survival (p < 0.0001) and a better quality of life (p < 0.05). Moreover, survival outcome was associated with a CLIP score < 3, extent of portal vein infiltration, well-differentiated tumor histology, prothrombin time, alkaline phosphatase, bilirubin, serum ferritin, and γ-glutamyltransferase (p < 0.01 each). Discussion: Rofecoxib added to octreotide treatment did not improve survival over octreotide treatment alone. Octreotide treatment, although without major side effects, cannot be recommended in general as monotherapy, unless the few patients responding can better be characterised. There may still be a role for combining octreotide with other emerging targeted therapies because of potentially synergistic modes of action.

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1 Survivors are definded as those patients who are still alive at the closure of the trial including a minimum follow-up of 6 months.

Gerhard Treiber, MD, AGAF

Department of Internal Medicine II, Saarland University Hospital

Kirrberger Str.

66421 Homburg

Germany

Phone: ++49/68 41/1 62 32 01

Fax: ++49/68 41/1 63 36 05

Email: ingtre@uniklinik-saarland.de