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Cyramza ® (ramucirumab)
Denna information är endast avsedd för sjukvårdspersonal verksam i Sverige och som svar på din fråga. Informationen nedan är på engelska
Krävs dosjusteringar av Cyramza® (ramucirumab) hos patienter med nedsatt njurfunktion?
Kliniska data tyder på att inga dosjusteringar krävs hos patienter med mild, måttlig eller gravt nedsatt njurfunktion.
Use in patients with mild, moderate and severe renal impairment
No dose reductions are recommended in patients with mild, moderate or severe renal impairment. This is based on clinical data. We did not perform formal studies with ramucirumab in patients with renal impairment.
Patients with normal renal function experienced a similar pharmacokinetic ramucirumab exposure as patients with mild, moderate or severe renal impairment, defined as mild renal impairment (calculated creatinine clearance [CrCl] ≥60 to <90 mL/min), moderate renal impairment (CrCl ≥30 to <60 mL/min), or severe renal impairment (CrCl <30 mL/min) as compared to patients with normal renal function (CrCl ≥90 mL/min).1,2
Use in end-stage renal disease and patients on dialysis
The use of ramucirumab in patients with end-stage renal disease and patients on dialysis has not been studied and no information is currently available.
A database search reveals a single case study on the use of ramucirumab in a patient on dialysis.3
The study concerns a 65-year-old man on hemodialysis (HD) who was diagnosed with gastric cancer at stage IIIb (pT3N2M0) and underwent a subtotal gastrectomy with D2 lymphadenectomy. After 8 cycles of adjuvant chemotherapy with capecitabine and oxaliplatin, abdominal computed tomography (CT) revealed multiple liver metastases from gastric cancer.
The patient was treated with ramucirumab without dose adjustment every 15-day at 8 mg/kg and weekly paclitaxel (80 mg/m2). The day after chemotherapy, the patient received hemodialysis and three times weekly after that.
After 2 and 4 cycles of chemotherapy, the patient had a partial response of the metastatic liver mass and a stable disease up to 12 cycles and without apparent adverse effect. However, after 14 cycles of chemotherapy, an abdominal CT revealed progression disease of multiple liver metastases and lymph nodes invasion.
The authors concluded that paclitaxel chemotherapy with ramucirumab can be administered without a dose reduction to patients with metastatic gastric cancer on hemodialysis in the same way as in patients with normal kidney function.3
Renal function requirements in our studies
Patients could participate in the clinical studies if they met the following adequate renal function definitions
- in the REGARD study: a serum creatinine ≤1.5 times the ULN or a creatinine clearance ≥40 mL/minute (as measured by 24-hour urine collection)4
- in the RAINBOW and REVEL studies: a serum creatinine ≤1.5 times the ULN or a calculated creatinine clearance ≥50 mL/minute (as calculated by Cockcroft-Gault or equivalent and/or as measured by 24-hour urine collection)5,6
- in the RAISE study: a serum creatinine clearance >50 mL/minute (as calculated by an equation endorsed by local institution guideline or as measured by 24-hour urine collection)7
- in the REACH-2 study: a calculated creatinine clearance ≥60 mL/minute (as calculated by Cockcroft-Gault or equivalent method such as 24-hour urine collection). Using radiolabeled markers to determine glomerular filtration rate was also acceptable,8 and
- in the RELAY study: a calculated creatinine clearance ≥50 mL/minute (as calculated by Cockcroft-Gault). If the value was below this parameter, then a 24-hour urine collection was to be done to rectify or ratify the estimated creatinine clearance.9
1Data on file, Eli Lilly and Company and/or one of its subsidiaries.
2Cyramza [summary of product characteristics]. Eli Lilly Nederland B.V., The Netherlands.
3Yang MJ, Choi YJ, Kim HJ, Kim DY, Seol YM. Treatment with Ramucirumab-paclitaxel in a metastatic gastric cancer patient undergoing hemodialysis: A case report. Medicine (Baltimore). 2021;100(7):e24795. doi:10.1097/MD.0000000000024795
4Fuchs CS, Tomasek J, Yong CJ, et al. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014;383(9911):31-39. http://dx.doi.org/10.1016/S0140-6736(13)61719-5
5Garon EB, Ciuleanu TE, Arrieta O, et al. Ramucirumab plus docetaxel versus placebo plus docetaxel for second-line treatment of stage IV non-small-cell lung cancer after disease progression on platinum-based therapy (REVEL): a multicentre, double-blind, randomised phase 3 trial. Lancet. 2014;384(9944):665-673. http://dx.doi.org/10.1016/S0140-6736(14)60845-X
6Wilke H, Muro K, Van Cutsem E, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014;15(11):1224-1235. http://dx.doi.org/10.1016/S1470-2045(14)70420-6
7Tabernero J, Yoshino T, Cohn AL, et al. Ramucirumab versus placebo in combination with second-line FOLFIRI in patients with metastatic colorectal carcinoma that progressed during or after first-line therapy with bevacizumab, oxaliplatin, and a fluoropyrimidine (RAISE): a randomised, double-blind, multicentre, phase 3 study. Lancet Oncol. 2015;16(5):499-508. http://dx.doi.org/10.1016/S1470-2045(15)70127-0
8Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282-296. http://dx.doi.org/10.1016/S1470-2045(18)30937-9
9Nakagawa K, Garon EB, Seto T, et al. Ramucirumab plus erlotinib in patients with untreated, EGFR-mutated, advanced non-small-cell lung cancer (RELAY): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(12):1655-1669. https://doi.org/10.1016/S1470-2045(19)30634-5
10Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. http://dx.doi.org/10.1159/000180580
Datum fӧr senaste ӧversyn August 15, 2019