Disertasi

Pengaruh Pemberian Pioglitazon terhadap Status Nutrisi pada Pasien Limfoma Malignum Non Hodgkin yang Mendapat Kemoterapi CHOP: Tinjauan terhadap Perubahan Kadar TNF-α, IL-1 beta, dan IL-6. = Effects of Pioglitazon on Nutritional Status in Patients with Non Hodgkin’s Malignant Limfoma who Received CHOP Chemoterapy: An Overview of Changes in Level TNF-α, IL-1 beta, and IL-6.

Latar Belakang. Gangguan nutrisi sering terjadi pada penderita kanker, baik sebelum pengobatan, selama pengobatan kanker ataupun pada kanker lanjut. Hal tersebut merupakan penyebab penting terjadinya peningkatan morbiditas dan mortalitas. Berbagai upaya dilakukan untuk memperbaiki status nutrisi pada pasien kanker, namun belum menampakkan hasil yang memuaskan. Pioglitazon, suatu derivat tiazolidindion, merupakan insulin sensitizer diharapkan dapat memperbaiki resistensi insulin pada pasien kanker, khususnya Lymphoma Malignum Non Hodgkin (LMNH). Belum pernah ada penelitian tentang peran Pioglitazon terhadap perbaikan status nutrisi dan perbaikan resistensi insulin serta pengaruhnya terhadap kadar TNF-α, IL-1β, dan IL-6 pada pasien LMNH. Tujuan. Menemukan alternatif terapi suportif pada penurunan berat badan akibat kanker, khususnya pada pasien LMNH, dengan pemberian Pioglitazon. Pemberian Pioglitazon diharapkan dapat memperbaiki status nutrisi, resistensi insulin, calorie intake, dan menurunkan kadar sitokin (TNF-α, IL-1β, IL-6). Metode Penelitian. Penelitian ini menggunakan desain eksperimental, acak, dan paralel terhadap pasien kanker LMNH sel B (CD20 (+)) stadium I-IV yang mendapat kemoterapi CHOP (cyclophosphamide, doxorubicin, vincristine, prednison) yang datang ke RS Kanker Dharmais Jakarta mulai November 2009 hingga Februari 2011. Subjek penelitian dibagi dua kelompok, yaitu perlakuan (pioglitazon) dan kontrol (plasebo). Penelitian dilakukan selama 4 siklus kemoterapi CHOP dengan pemantauan parameter klinis (calorie intake, body mass index/BMI) dan parameter laboratoris (HOMA-IR index, TNF- α, IL-1β, dan IL-6) yang diukur setelah siklus kemoterapi ke-2 dan ke-4. Hasil. Pada kelompok perlakuan didapatkan kecenderungan perbaikan status nutrisi, perbaikan resistensi insulin, perbaikan calorie intake, dan kecenderungan penurunan kadar sitokin (TNF-α, IL-1β, dan IL-6) bila dibandingkan dengan kelompok kontrol. Tidak ditemukan adanya efek samping hipoglikemia, gangguan fungsi ginjal, fungsi hati yang bermakna pada seluruh pasien selama dalam penelitian. Simpulan. Pemberian Pioglitazon belum terbukti namun cenderung memperbaiki status nutrisi pada pasien LMNH yang mendapat kemoterapi CHOP. Pemberian Pioglitazon terbukti memperbaiki resistensi insulin dan calorie intake, namun belum terbukti dapat menurunkan kadar sitokin (TNF-α, IL-1β, dan IL-6). Tidak ditemukan hipoglikemia, gangguan fungsi ginjal maupun fungsi hati selama dalam penelitian
Kata kunci: IL-1β, IL-6, Kemoterapi CHOP, LMNH, Pioglitazon, status nutrisi, TNF-α.



Background. Nutritional disorders frequently occur in cancer patients, both before treatment, during cancer treatment or in advanced cancer. This is an important cause of increased morbidity and mortality. Various attempts were made to improve the nutritional status in cancer patients, but has not revealed a satisfactory result. Pioglitazone, a tiazolidindion derivative, an insulin sensitizer is expected to improve insulin resistance in patients with cancer, particularly Non-Hodgkin's Malignant Lymphoma (NHML). There has never been any research on the role of pioglitazone on the improvement of nutritional status and improvement of insulin resistance and its influence on levels of TNF-α, IL-1β, and IL-6 in patients with NHML. Objectives. Finding alternative supportive therapy on weight loss due to cancer, particularly in patients NHML, with the provision of pioglitazone. Giving pioglitazone is expected to improve nutritional status, insulin resistance, calorie intake, and lower levels of cytokines (TNF-α, IL-1β, IL-6). Methods. This study uses an experimental , randomized, and parallel design to the cancer patients NHML B cell (CD20 (+)) stage I-IV who received CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone) who came to Jakarta Dharmais Cancer Hospital from November 2009 to February 2011. Research subjects were divided into two groups, namely the treatment (pioglitazone) and control (placebo). The study was conducted during 4 cycles of CHOP chemotherapy with monitoring of clinical parameters (calorie intake, body mass index/BMI) and laboratory parameters (HOMA-IR index, TNF-α, IL-1β and IL-6) measured after the second and fourth cycles of chemotherapy. Results. In the treatment group there was a trend toward improvement in nutritional status, improvement of insulin resistance, improved calorie intake, and the trend to decline in levels of cytokines (TNF-α, IL-1β and IL-6) when compared with the control group. There are no known side effects of hypoglycemia, impaired renal function, liver function in all patients during the study. Summary. Giving pioglitazone although has not been proven but tends to improve nutritional status in NHML patients who received CHOP chemotherapy. Provision of pioglitazone is shown to improve insulin resistance and calorie intake, but has not been proven to reduce the levels of cytokines (TNF-α, IL-1β and IL-6). There were no hypoglycemia, impaired renal function and liver function during the study.
Keywords: CHOP Chemoterapy, IL-1β, IL-6, NHML, nutritional status, Pioglitazone, TNF-α