High‐dose methotrexate‐induced nephrotoxicity in patients with osteosarcoma

High‐dose methotrexate (HDMTX)‐induced renal dysfunction can be life threatening, because it delays methotrexate (MTX) excretion, thereby exacerbating the other toxicities of MTX. HDMTX‐induced nephrotoxicity has been managed with high‐dose leucovorin, dialysis‐based methods of MTX removal, thymidine, and with the recombinant enzyme, carboxypeptidase‐G2 (CPDG2), which cleaves MTX to inactive metabolites. The objectives of the current study were to estimate the current incidence of HDMTX‐induced renal dysfunction in patients with osteosarcoma and to compare the efficacy and recovery of renal function for dialysis‐based methods of MTX removal with treatment using CPDG2.

[1]  H. Jürgens,et al.  Toxicity associated with combination chemotherapy for osteosarcoma: A report of the cooperative osteosarcoma study (COSS 80) , 2004, Journal of Cancer Research and Clinical Oncology.

[2]  A. Craft,et al.  A comparison of two short intensive adjuvant chemotherapy regimens in operable osteosarcoma of limbs in children and young adults: the first study of the European Osteosarcoma Intergroup. , 1992, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  S. Ferrari,et al.  Neoadjuvant chemotherapy for extremity osteosarcoma--preliminary results of the Rizzoli's 4th study. , 1998, Acta oncologica.

[4]  S. Ferrari,et al.  Primary chemotherapy and delayed surgery for non-metastatic telangiectatic osteosarcoma of the extremities. Results in 28 patients. , 1994, European journal of cancer.

[5]  S. Ferrari,et al.  Predictive factors of histologic response to primary chemotherapy in osteosarcoma of the extremity: study of 272 patients preoperatively treated with high-dose methotrexate, doxorubicin, and cisplatin. , 1998, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[6]  P. Adamson,et al.  Carboxypeptidase‐G2 rescue in a patient with high dose methotrexate‐induced nephrotoxicity , 1995, Cancer.

[7]  A monocentric therapy study: an approach to optimize the results of the treatment of osteosarcoma by protocols based upon HDMTX, associated with systematic conservative surgery. , 1993, Cancer treatment and research.

[8]  S. Ferrari,et al.  The importance of dose-intensity in neoadjuvant chemotherapy of osteosarcoma: a retrospective analysis of high-dose methotrexate, cisplatinum and adriamycin used preoperatively. , 1990, Journal of chemotherapy.

[9]  M. Marangolo,et al.  Neoadjuvant chemotherapy for nonmetastatic osteosarcoma of the extremities. , 1991, Clinical orthopaedics and related research.

[10]  P. Piedbois,et al.  [Effectiveness of hemodialysis in a case of acute methotrexate poisoning]. , 1990, Presse medicale.

[11]  T. Lion,et al.  Successful carboxypeptidase G2 rescue in delayed methotrexate elimination due to renal failure. , 1995, Pediatric hematology and oncology.

[12]  P. Adamson,et al.  Pharmacokinetics and metabolism of the methotrexate metabolite 2, 4-diamino-N(10)-methylpteroic acid. , 2000, The Journal of pharmacology and experimental therapeutics.

[13]  P. Leavey,et al.  Effective removal of methotrexate by high-flux hemodialysis , 2002, Pediatric Nephrology.

[14]  W. Ebell,et al.  Neoadjuvant chemotherapy for osteogenic sarcoma: results of a Cooperative German/Austrian study. , 1984, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  H. Jürgens,et al.  [Results of treatment in primary disseminated osteosarcoma. Analysis of the follow-up of patients in the cooperative osteosarcoma studies COSS-80 and COSS-82]. , 1989, Onkologie.

[16]  G. Henze,et al.  Schwere renale Methotrexat-Ausscheidungsstörung nach Hochdosis-Therapie , 1994 .

[17]  J. Greil,et al.  Continuous plasma resin perfusion for detoxification of methotrexate , 1997, European Journal of Pediatrics.

[18]  P. Ivanovich,et al.  Hemoperfusion for methotrexate removal , 1978, Clinical pharmacology and therapeutics.

[19]  D. Frappaz,et al.  [Methotrexate poisoning: value of exchange transfusion]. , 1987, Pediatrie.

[20]  S. Wall,et al.  Effective clearance of methotrexate using high-flux hemodialysis membranes. , 1996, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[21]  P. Picci,et al.  Primary chemotherapy and delayed surgery (neoadjuvant chemotherapy) for osteosarcoma of the extremities the istituto rizzoli experience in 127 patients treated preoperatively with intravenous methotrexate (high versus moderate doses) and intraarterial cisplatin , 1990, Cancer.

[22]  S. Rosenberg,et al.  Use of plasma pharmacokinetics to predict and prevent methotrexate toxicity. , 1977, The New England journal of medicine.

[23]  C. Théodore,et al.  Successful rescue in a patient with high dose methotrexate-induced nephrotoxicity and acute renal failure. , 1998, Leukemia & lymphoma.

[24]  C. Ichai,et al.  Removal of methotrexate by continuous venovenous hemodiafiltration. , 1995, Contributions to nephrology.

[25]  J. Høie,et al.  Extremity and non-extremity high-grade osteosarcoma -- the Norwegian Radium Hospital experience during the modern chemotherapy era. , 1996, Acta oncologica.

[26]  J. Rossi,et al.  Carboxypeptidase G2 Rescue in Delayed Methotrexate Elimination in Renal Failure , 2000, Leukemia & lymphoma.

[27]  S. Bielack,et al.  Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group's protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs. , 1998, Annals of oncology : official journal of the European Society for Medical Oncology.

[28]  P. Adamson,et al.  Carboxypeptidase-G2, thymidine, and leucovorin rescue in cancer patients with methotrexate-induced renal dysfunction. , 1997, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[29]  B. Chabner,et al.  7-Hydroxymethotrexate as a urinary metabolite in human subjects and rhesus monkeys receiving high dose methotrexate. , 1976, The Journal of clinical investigation.

[30]  S. Ferrari,et al.  Neoadjuvant chemotherapy for osteosarcoma of the extremity in patients in the fourth and fifth decade of life. , 1998, Oncology reports.

[31]  I. Elomaa,et al.  The treatment of osteosarcoma: present trends. The Scandinavian Sarcoma Group experience. , 1992, Annals of oncology : official journal of the European Society for Medical Oncology.

[32]  T. Atkinson,et al.  Molecular cloning of the Pseudomonas carboxypeptidase G2 gene and its expression in Escherichia coli and Pseudomonas putida , 1983, Journal of bacteriology.

[33]  H. Makino,et al.  A case of methotrexate-induced acute renal failure successfully treated with plasma perfusion and sequential hemodialysis. , 1995, Nephron.

[34]  G. Milano,et al.  Removal of methotrexate by hemodiafiltration , 2004, Cancer Chemotherapy and Pharmacology.

[35]  H. Jürgens,et al.  Neoadjuvant chemotherapy of osteosarcoma: results of a randomized cooperative trial (COSS-82) with salvage chemotherapy based on histological tumor response. , 1988, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[36]  C. R. Pinkerton,et al.  CHARCOAL HAEMOPERFUSION AND METHOTREXATE TOXICITY , 1986, The Lancet.

[37]  S. Bielack,et al.  Osteosarcoma of the trunk treated by multimodal therapy: experience of the Cooperative Osteosarcoma study group (COSS). , 1995, Medical and pediatric oncology.

[38]  Willem Boogerd,et al.  Successful rescue with leucovorin and thymidine in a patient with high-dose methotrexate induced acute renal failure , 2001, Cancer Chemotherapy and Pharmacology.

[39]  D. Frappaz,et al.  [Hemoperfusion on charcoal and hemodialysis in acute poisoning caused by methotrexate]. , 1988, Presse medicale.

[40]  M. Link,et al.  Methotrexate-induced renal impairment: clinical studies and rescue from systemic toxicity with high-dose leucovorin and thymidine. , 1983, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  P. Picci,et al.  Complications and surgical indications in 144 cases of nonmetastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy. , 1993, Clinical orthopaedics and related research.

[42]  S. Ferrari,et al.  Osteogenic sarcoma of the extremity with detectable lung metastases at presentation , 1997, Cancer.

[43]  S. Pond,et al.  Survival After Unexpected High Serum Methotrexate Concentrations in a Patient with Osteogenic Sarcoma , 1990, Drug safety.

[44]  S. Ferrari,et al.  Nonmetastatic Osteosarcoma of the Extremity: Results of a Neoadjuvant Chemotherapy Protocol (IOR/OS-3) with High-dose Methotrexate, Intraarterial or Intravenous Cisplatin, Doxorubicin, and Salvage Chemotherapy Based on Histologic Tumor Response , 1999, Tumori.

[45]  J. V. van Horn,et al.  Adriamycin-methotrexate high dose versus adriamycin-methotrexate moderate dose as adjuvant chemotherapy for osteosarcoma of the extremities: a randomized study. , 1986, European journal of cancer & clinical oncology.

[46]  P. Canal,et al.  Acute renal failure after high-dose methotrexate therapy. Role of hemodialysis and plasma exchange in methotrexate removal. , 1989, Nephron.

[47]  A. Stenwig,et al.  Treatment of osteosarcoma of the extremities with the T-10 protocol, with emphasis on the effects of preoperative chemotherapy with single-agent high-dose methotrexate: a Scandinavian Sarcoma Group study. , 1991, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[48]  W. Bleyer,et al.  Methotrexate: clinical pharmacology, current status and therapeutic guidelines. , 1977, Cancer treatment reviews.

[49]  P. Picci,et al.  Neoadjuvant chemotherapy for osteosarcoma of the extremities: the Rizzoli Institute experience. , 1990, La Chirurgia degli organi di movimento.

[50]  G. Jackson,et al.  Severe renal toxicity due to intermediate-dose methotrexate , 1989, Cancer Chemotherapy and Pharmacology.

[51]  S. Ferrari,et al.  Long-term outcome for patients with nonmetastatic osteosarcoma of the extremity treated at the istituto ortopedico rizzoli according to the istituto ortopedico rizzoli/osteosarcoma-2 protocol: an updated report. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[52]  R. Bast,et al.  High dose methotrexate with leucovorin rescue. Rationale and spectrum of antitumor activity. , 1980, The American journal of medicine.

[53]  S. Bielack,et al.  [Neoadjuvant chemotherapy of osteosarcoma. Preliminary results of the cooperative COSS-86 osteosarcoma study]. , 1991, Klinische Padiatrie.

[54]  D. Machin,et al.  Received dose and dose-intensity of chemotherapy and outcome in nonmetastatic extremity osteosarcoma. European Osteosarcoma Intergroup. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[55]  S. Ferrari,et al.  Intra-arterial versus intravenous cisplatinum (in addition to systemic Adriamycin and high dose methotrexate) in the neoadjuvant treatment of osteosarcoma of the extremities. results of a randomized study. , 1996, Journal of chemotherapy.

[56]  M. Salzer-Kuntschik,et al.  Ergebnisse der Studien COSS-77 und COSS-80 für die adjuvante Chemotherapie bei Osteosarkom der Extremitäten* , 1985 .

[57]  A. McIvor Charcoal hemoperfusion and methotrexate toxicity. , 1991, Nephron.

[58]  S. Ferrari,et al.  Neoadjuvant chemotherapy for osteosarcoma of the extremities with synchronous lung metastases: treatment with cisplatin, adriamycin and high dose of methotrexate and ifosfamide. , 2000, Oncology reports.

[59]  P. Adamson,et al.  Dihydrofolate reductase enzyme inhibition assay for plasma methotrexate determination using a 96-well microplate reader. , 1999, Clinical chemistry.

[60]  S. Leyvraz,et al.  Effect of intraarterial versus intravenous cisplatin in addition to systemic doxorubicin, high‐dose methotrexate, and ifosfamide on histologic tumor response in osteosarcoma (study COSS‐86) , 1990, Cancer.

[61]  S. Howell,et al.  Hemodialysis and enzymatic cleavage of methotrexate in man. , 1978, European journal of cancer.

[62]  D. V. Von Hoff,et al.  Incidence of drug-related deaths secondary to high-dose methotrexate and citrovorum factor administration. , 1977, Cancer treatment reports.

[63]  A. Langleben,et al.  Case report: management of methotrexate toxicity in an anephric patient. , 1982, Clinical and investigative medicine. Medecine clinique et experimentale.

[64]  N. Haim,et al.  Methotrexate-related deaths in patients previously treated with cis-diamminedichloride platinum , 2004, Cancer Chemotherapy and Pharmacology.

[65]  N. Jaffe,et al.  Pediatric osteosarcoma: therapeutic strategies, results, and prognostic factors derived from a 10-year experience. , 1990, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[66]  M. Marangolo,et al.  The treatment of localized osteosarcoma of the extremities: the Italian experience. Studies of the National Research Council. , 1992, Annals of oncology : official journal of the European Society for Medical Oncology.

[67]  P. Meyers,et al.  High-dose leucovorin as sole therapy for methotrexate toxicity. , 1999, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[68]  M. Scarborough,et al.  Dose-Intense Ifosfamide/Doxorubicin/Cisplatin Based Chemotherapy for Osteosarcoma in Adults , 2002, American journal of clinical oncology.

[69]  C. Fábián,et al.  Use of charcoal hemoperfusion with sequential hemodialysis to reduce serum methotrexate levels in a patient with acute renal insufficiency. , 1987, The American journal of medicine.

[70]  S. Ferrari,et al.  Primary chemotherapy and delayed surgery for nonmetastatic osteosarcoma of the extremities. Results in 164 patients preoperatively treated with high doses of methotrexate followed by cisplatin and doxorubicin , 1993, Cancer.

[71]  R. Kotz,et al.  [Results of the COSS-77 and COSS-80 studies on adjuvant chemotherapy in osteosarcoma of the extremities]. , 1985, Klinische Padiatrie.

[72]  M. Christian,et al.  Clinical use of thymidine as a rescue agent from methotrexate toxicity , 1991, Investigational New Drugs.

[73]  W. Evans,et al.  Adjuvant chemotherapy for osteosarcoma of the extremity long‐term results of two consecutive prospective protocol studies , 1990, Cancer.

[74]  J. Lankelma,et al.  The role of 7-hydroxymethotrexate during methotrexate anti-cancer therapy. , 1980, Cancer letters.

[75]  D. Frappaz,et al.  Hémoperfusion sur charbon activé et hémodialyse dans l'intoxication aiguë au méthotrexate. , 1988 .

[76]  I. Fleming,et al.  Osteosarcoma studies at St. Jude Children's Research Hospital from 1968 through 1990. , 1993, Cancer treatment and research.

[77]  R. Melton,et al.  Purification and properties of carboxypeptidase G2 from Pseudomonas sp. strain RS-16. Use of a novel triazine dye affinity method. , 1985, European journal of biochemistry.

[78]  P. Arnaud,et al.  Dose escalation with pharmacokinetics monitoring in methotrexate chemotherapy of osteosarcoma. , 1995, Anticancer research.

[79]  J. Shuster,et al.  The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. , 1986, The New England journal of medicine.

[80]  W. Evans,et al.  Recovery from toxicity associated with high-dose methotrexate: prognostic factors. , 1977, Cancer treatment reports.

[81]  R. Souhami,et al.  Randomised trial of two regimens of chemotherapy in operable osteosarcoma: a study of the European Osteosarcoma Intergroup , 1997, The Lancet.

[82]  S. Rosenberg,et al.  Methotrexate and hemodialysis. , 1977, Annals of internal medicine.

[83]  R. Schilsky,et al.  High-dose methotrexate: a critical reappraisal. , 1987, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[84]  R. Donehower,et al.  Presence of 2,4‐diamino‐N10‐methylpteroic acid after high‐dose methotrexate , 1979, Clinical pharmacology and therapeutics.

[85]  M. Relling,et al.  Removal of methotrexate, leucovorin, and their metabolites by combined hemodialysis and hemoperfusion , 1988, Cancer.

[86]  Y. Yamano,et al.  Severe complications after high-dose methotrexate treatment. , 1995, Acta oncologica.

[87]  I. Djerassi,et al.  Removal of methotrexate by filtration-adsorption using charcoal filters or by hemodialysis. , 1977, Cancer treatment reports.

[88]  G. Hortobagyi,et al.  High-dose methotrexate for advanced breast cancer. , 1979, Cancer treatment reports.

[89]  P. Harden,et al.  Methotrexate removal during haemodialysis in a patient with advanced laryngeal carcinoma , 1996, Cancer Chemotherapy and Pharmacology.

[90]  W. Bleyer,et al.  Methotrexate-induced renal failure and ineffectiveness of peritoneal dialysis. , 1978, Archives of internal medicine.

[91]  N. Jaffe,et al.  Renal toxicity with cumulative doses of cis‐diamminedichloroplatinum‐II in pediatric patients with osteosarcoma. Effect on creatinine clearance and methotrexate excretion , 1987, Cancer.