Theophylline, een middeltje verwant aan caffeïne beperkt significant bijwerkingen van op cisplatin gebaseerde chemokuren en beschermt de nieren tijdens chemokuren bij patiënten met verschillende kankersoorten

8 juli 2011: ik ben kanker-actueel aan het herzien en onderstaand artikel is nog steeds relevant en informatief dus laat dit staan.

9 augustus 2005: Bron: J Am Soc Nephrol. 2005 Feb;16(2):452-8. Epub 2004 Dec 8.

Theophylline (een metaboliet van cafeine) gaat in gerandomiseerd onderzoek verslechtering nierfunctie door chemo met cisplatin significant tegen. Blijkt uit placebo gerandomiseerde studie bij niet genoemd aantal kankerpatiënten met verschillende vormen van kanker. Hier het abstract van deze studie uitgevoerd in het academisch ziekenhuis van Göttingen Duitsland en daaronder een in 2000 gepubliceerde studie (dubbelblind gerandomiseerd) waar Thephyline bij pasgeboren babies met een vorm van perinatal asphyxia (sorry durf dat niet letterlijk te vertalen) ook significant de nierfunctie verbeterde. Dit natuurlijke middeltje heeft dus sterk therapeutische kwaliteiten

Nephroprotection by theophylline in patients with cisplatin chemotherapy: a randomized, single-blinded, placebo-controlled trial.

Benoehr P, Krueth P, Bokemeyer C, Grenz A, Osswald H, Hartmann JT.

Department of Nephrology and Rheumatology, Georg-August-University, Robert-Koch Strasse 40, 37075 Gottingen, Germany. pbenoeh@gwdg.de

The aim of the present study was to assess the possible prevention of cisplatin-induced impairment of GFR by theophylline in patients with various malignancies. The trial design was parallel, randomized, single blinded, and placebo controlled. Patients received cisplatin at a dosage of 50 mg/m(2) either combined with etoposide, ifosfamide, and epirubicin or with paclitaxel and 5-fluorouracil/folinic acid with the usual precautions, including a standard hydration scheme before application of cisplatin in both arms. In the control arm, placebo was administered; in the verum arm, patients received theophylline in a loading dose of 4 mg/kg intravenously over 30 min before cisplatin, followed by 0.4 mg/kg per min over a minimum of 6 h, and then 350 mg three times daily orally for 4 consecutive days after completion of chemotherapy. GFR of each patient was assessed by renal clearance of inulin within 3 d before and at day 5 after cisplatin chemotherapy. Despite usual precautions, patients in the placebo group had a 21% decrease (range, 11 to 31%) of inulin clearance after a single cycle of cisplatin-containing chemotherapy (92.9 +/- 3.4 versus 71.8 +/- 3.5 ml/min; P < 0.01). Patients who received theophylline had no deterioration of GFR (91.5 +/- 3.7 versus 90.0 +/- 3.8 ml/min; P > 0.05). No adverse effects have been observed during theophylline application. Conventional precautions such as hydration and osmotic diuresis cannot prevent a significant decrease of GFR after a single cycle of cisplatin-containing chemotherapy. The prophylactic application of theophylline as an intravenous loading dose and oral maintenance regimen may preserve kidney function in terms of GFR.

Publication Types:
Clinical Trial
Randomized Controlled Trial

PMID: 15590762 [PubMed - indexed for MEDLINE]

Pediatrics. 2000 Apr;105(4):E45.

A randomized, double-blind, placebo-controlled trial of the effects of prophylactic theophylline on renal function in term neonates with perinatal asphyxia.

Jenik AG, Ceriani Cernadas JM, Gorenstein A, Ramirez JA, Vain N, Armadans M, Ferraris JR.
Department of Pediatrics of the Hospital Italiano, Buenos Aires, Argentina. ajenik@drwebsa.com.ar

BACKGROUND: The kidney is the most damaged organ in asphyxiated full-term infants. Experiments in rabbits and rats have shown that renal adenosine acts as a vasoconstrictive metabolite in the kidney after hypoxemia and/or ischemia, contributing to the fall in glomerular filtration rate (GFR) and filtration fraction. Vasoconstriction produced by adenosine can be inhibited by the nonspecific adenosine receptor antagonist, theophylline. Gouyon and Guignard performed studies in newborn and adult rabbits subjected to normocapnic hypoxemia. Their results clearly showed that the hypoxemia-induced drop in GFR could be avoided by the administration of low doses of theophylline.

OBJECTIVE: This study was designed to determine whether theophylline could prevent and/or ameliorate renal dysfunction in term neonates with perinatal asphyxia.

SETTING: Buenos Aires, Argentina.

STUDY DESIGN: We randomized 51 severe asphyxiated term infants to receive intravenously a single dose of either theophylline (8 mg/kg; study group: n = 24) or placebo (control group: n = 27) during the first 60 minutes of life. The 24-hour fluid intake and the urine volumes formed were recorded during the first 5 days of life. Daily volume balances (water output/input ratio and weights) were determined. Severe renal dysfunction was defined as serum creatinine elevated above 1.50 mg/dL, for at least 2 consecutive days after a fluid challenge, or rising levels of serum creatinine (.3 mg/dL/day). The GFR was estimated during the second to third days of life by endogenous creatinine clearance (mL/minute/1.73 m2) and using Schwartz's formula: GFR (mL/minute/1.73 m2) =.45 x length (cm)/plasma creatinine (mg/100 mL) during the first 5 days of life. Tubular performance was assessed as the concentration of beta2-microglobulin (beta2M) determined by enzyme immunoassay, on the first voided urine 12 hours after theophylline administration. The statistical analysis for the evaluation of the differences between the groups was performed with Student's t and chi(2) tests as appropriate.

RESULTS: During the first day of life, the 24-hour fluid balance was significantly more positive in the infants receiving placebo compared with the infants receiving theophyline. Over the next few days, the change in fluid balance favored the theophyline group. Significantly higher mean plasma values were recorded in the placebo group from the second to the fifth days of life. Severe renal dysfunction was present in 4 of 24 (17%) infants of the theophylline group and in 15 of 27 (55%) infants of the control group (relative risk:.30; 95% confidence interval:.12-.78). Mean endogenous creatinine clearance of the theophylline group was significantly increased compared with the creatinine clearance in infants receiving placebo (21.84 +/- 7.96 vs 6.42 +/- 4.16). The GFR (estimated by Schwartz's formula) was markedly decreased in the placebo group. Urinary beta2M concentrations were significantly reduced in the theophylline group (5.01 +/- 2.3 mg/L vs 11.5 +/- 7.1 mg/L). Moreover, 9 (33%) patients of the theophylline group versus 20 (63%) infants of the control group had urinary beta2M above the normal limit (<.018). There was no difference in the severity of the asphyxia between infants belonging to the theophylline and control groups in regards of Portman's score. Except for renal involvement, a similar frequency of multiorganic dysfunction, including neurologic impairment, was observed in both groups. The theophylline group achieved an average serum level of 12.7 microg/mL (range: 7.5-18.9 microg/mL) at 36 to 48 hours of live versus traces (an average serum level of .87 microg/mg) in the placebo group.

CONCLUSIONS: Our data suggest that prophylactic theophylline, given early after birth, has beneficial effects on reducing the renal dysfunction in asphyxiated full-term infants. (ABSTRACT TRUNCATED)

Publication Types:
Clinical Trial
Multicenter Study
Randomized Controlled Trial

PMID: 10742366 [PubMed - indexed for MEDLINE]

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