Pioglitazone therapy in progressive differentiated thyroid carcinoma

 

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Summary

Aim: Rosiglitazone achieved promising results in progressive differentiated thyroid carcinoma (DTC) with redifferentiative and antiproliferative effects, but has been taken off the market. Thus we evaluated another glitazone, pioglitazone, expecting similar positive results. Patient, materials, methods: Five patients with progressive DTC and no or only negligible iodine uptake were enrolled. Oral pioglitazone treatment was applied for 6 months. The re-differentiative effect was assessed by ¹²⁴I-NaI PET/CT dosimetry and the anti-proliferative effect by ¹⁸F-FDG PET/CT imaging. Results: A redifferentiative effect of pioglitazone could not be shown. Lesion dosimetry indicated that 3/5 patients had unchanged no lesion absorbed dose per administered activity (LDpA) in any tumour lesion, 2/5 patients had a deterioration of LDpA within some lesions, thus radioiodine therapy was not performed in any patient. Volumetric analysis, using RECIST criteria, revealed progressive disease in 3/5 patients and stable disease in 2/5 patients. Metabolic changes, using EORTC criteria, revealed 3/5 patients with progressive metabolic disease, 1/5 patient with stable metabolic disease and 1/5 patients with partial metabolic response. The medication was well-tolerated, and no patient developed clinically important toxicity associated with the treatment. Conclusion: Pioglitazone revealed some positive effects in radioiodine negative and progressive DTC patients but it did not fulfill the expectations given by the results of rosiglitazone therapy.

Zusammenfassung

Ziel: Die Rosiglitazon-Therapie beim differenzierten Schilddrüsenkarzinom (DTC) war durch redifferenzierende und antiproliferative Eigenschaften vielversprechend, jedoch wurde das Präparat vom Markt genommen. Daher evaluierten wir ein weiteres Glitazon, das Pioglitazon in der Erwartung ähnlicher Ergebnisse. Patienten, Methode: Fünf Patienten mit fortgeschrittenem DTC und fehlendem oder vernachlässigbarem Iod-Uptake wurden eingeschlossen und erhielten eine orale Pioglitazon- Behandlung über sechs Monate. Die rediffernzierenden Effekte wurden mit ¹²⁴I-NaIPET/ CT und die antiproliferativen Effekte mit ¹⁸F-FDG-PET/CT überprüft. Ergebnisse: Redifferenzierung durch die Pioglitazon-Therapie wurde nicht beobachtet. Die Läsionsdosimetrie zeigte unverändert in den Tumorläsionen keine erzielbare Läsionsdosis pro applizierter Aktivität (LDpA) in 3/5 Patienten und eine Verschlechterung der LDpA in 2/5 Patienten. Folglich wurde bei keinem Patienten eine Radioiodtherapie durchgeführt. Tumorgrößen-Veränderungen gemäß RECIST 1.1 ergaben bei 3/5 Patienten eine progrediente Erkrankung und bei 2/5 Patienten eine „stable disease“. Nach EORTC-Kriterien hatten 3/5 Patienten eine progrediente Erkrankung, 1/5 Patienten eine „stable disease“ und 1/5 Patienten eine „partial metabolic response“. Pioglitazon wurde gut vertragen, kein Patient erlitt eine klinisch relevante, durch die Behandlung verursachte Toxizität. Schlussfolgerung: Die Pioglitazon-Therapie erzielte nur einen geringen positiven Effekt bei der Therapie des Radioiod-negativen fortgeschrittenen DTC und erfüllte somit nicht die Erwartungen, die durch die Rosiglitazon-Therapie bestanden.

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