Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: A non-randomised phase 2 clinical trial

The Lancet Oncology

Volumn 16, Issue 1, 2015, Pages 98-107

  Grignani, Giovanni ^a   Palmerini, Emanuela ^b   Ferraresi, Virginia ^c   D'Ambrosio, Lorenzo ^a,d   Bertulli, Rossella ^e   Asaftei, Sebastian Dorin ^f   Tamburini, Angela ^g   Pignochino, Ymera ^a,d   Sangiolo, Dario ^a,d   Marchesi, Emanuela ^b   Capozzi, Federica ^a,d   Biagini, Roberto ^c   Gambarotti, Marco ^b   Fagioli, Franca ^f   Casali, Paolo Giovanni ^e   Picci, Piero ^b   Ferrari, Stefano ^b   Aglietta, Massimo ^a,d  

^a CANDIOLO CANCER INSTITUTE   (Italy)

^b RIZZOLI ORTHOPAEDIC INSTITUTE   (Italy)

^c REGINA ELENA NATIONAL CANCER INSTITUTE   (Italy)

^d UNIVERSITY OF TURIN   (Italy)

^e NATIONAL CANCER INSTITUTE   (Italy)

^f CITTÀ DELLA SALUTE E DELLA SCIENZA HOSPITAL   (Italy)

^g UNIVERSITY OF FLORENCE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

AMINOTRANSFERASE; AMYLASE; BILIRUBIN; CISPLATIN; CREATINE KINASE; CREATININE; DOXORUBICIN; EVEROLIMUS; GAMMA GLUTAMYLTRANSFERASE; IFOSFAMIDE; METHOTREXATE; SORAFENIB; TRIACYLGLYCEROL LIPASE; ANTINEOPLASTIC AGENT; CARBANILAMIDE DERIVATIVE; MTOR PROTEIN, HUMAN; NICOTINAMIDE; RAPAMYCIN; TARGET OF RAPAMYCIN KINASE;

ABDOMINAL CRAMP; ACNE; ADULT; ANEMIA; ARTHRALGIA; ARTICLE; BLEEDING; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER RECURRENCE; CLINICAL ARTICLE; CONSTIPATION; COUGHING; DIARRHEA; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG SAFETY; DRUG WITHDRAWAL; DYSPHAGIA; FATIGUE; FEBRILE NEUTROPENIA; FEMALE; HEADACHE; HEART EJECTION FRACTION; HUMAN; HYPERCHOLESTEROLEMIA; HYPERGLYCEMIA; HYPERTENSION; HYPERTRIGLYCERIDEMIA; HYPOKALEMIA; HYPOMAGNESEMIA; HYPOPHOSPHATEMIA; INFECTION; INTENTION TO TREAT ANALYSIS; LEUKOPENIA; LOCAL SKIN REACTION; LYMPHOCYTOPENIA; MALE; MYALGIA; NAUSEA; NEUTROPENIA; ORAL MUCOSITIS; OSTEOSARCOMA; PATIENT HISTORY OF CHEMOTHERAPY; PHASE 2 CLINICAL TRIAL; PNEUMOTHORAX; PRIORITY JOURNAL; PROGRESSION FREE SURVIVAL; PRURITUS; RASH; THROMBOCYTOPENIA; TREATMENT OUTCOME; TREATMENT RESPONSE; UNSPECIFIED SIDE EFFECT; VOMITING; WEIGHT REDUCTION; XEROSIS; ADOLESCENT; ANALOGS AND DERIVATIVES; ANTAGONISTS AND INHIBITORS; BONE NEOPLASMS; CANCER GRADING; CLINICAL TRIAL; DISEASE COURSE; DISEASE FREE SURVIVAL; ENZYMOLOGY; ITALY; KAPLAN MEIER METHOD; METABOLISM; MIDDLE AGED; MULTICENTER STUDY; PATHOLOGY; SECONDARY; TIME; YOUNG ADULT;

ADOLESCENT; ADULT; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; BONE NEOPLASMS; DISEASE PROGRESSION; DISEASE-FREE SURVIVAL; FEMALE; HUMANS; INTENTION TO TREAT ANALYSIS; ITALY; KAPLAN-MEIER ESTIMATE; MALE; MIDDLE AGED; NEOPLASM GRADING; NIACINAMIDE; OSTEOSARCOMA; PHENYLUREA COMPOUNDS; SIROLIMUS; TIME FACTORS; TOR SERINE-THREONINE KINASES; TREATMENT OUTCOME; YOUNG ADULT;

EID: 84926081430     PISSN: 14702045     EISSN: 14745488     Source Type: Journal    
DOI: 10.1016/S1470-2045(14)71136-2     Document Type: Article

References (43)

1. Gatta G, van der Zwan JM, Casali PG, et al. Rare cancers are not so rare: the rare cancer burden in Europe. Eur J Cancer 2011, 47:2493-2511. the RARECARE working group.
2. Meyers PA, Schwartz CL, Krailo MD, et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival-a report from the Children's Oncology Group. J Clin Oncol 2008, 26:633-638. the Children's Oncology Group.
3. Bielack SS, Kempf-Bielack B, Delling G, et al. Prognostic factors in high-grade osteosarcoma of the extremities or trunk: an analysis of 1,702 patients treated on neoadjuvant cooperative osteosarcoma study group protocols. J Clin Oncol 2002, 20:776-790.
4. Kempf-Bielack B, Bielack SS, Jürgens H, et al. Osteosarcoma relapse after combined modality therapy: an analysis of unselected patients in the Cooperative Osteosarcoma Study Group (COSS). J Clin Oncol 2005, 23:559-568.
5. Ferrari S, Briccoli A, Mercuri M, et al. Postrelapse survival in osteosarcoma of the extremities: prognostic factors for long-term survival. J Clin Oncol 2003, 21:710-715.
6. Harris MB, Cantor AB, Goorin AM, et al. Treatment of osteosarcoma with ifosfamide: comparison of response in pediatric patients with recurrent disease versus patients previously untreated: a Pediatric Oncology Group study. Med Pediatr Oncol 1995, 24:87-92.
7. Rodríguez-Galindo C, Daw NC, Kaste SC, et al. Treatment of refractory osteosarcoma with fractionated cyclophosphamide and etoposide. J Pediatr Hematol Oncol 2002, 24:250-255.
8. Berger M, Grignani G, Ferrari S, et al. Phase 2 trial of two courses of cyclophosphamide and etoposide for relapsed high-risk osteosarcoma patients. Cancer 2009, 115:2980-2987.
9. Navid F, Willert JR, McCarville MB, et al. Combination of gemcitabine and docetaxel in the treatment of children and young adults with refractory bone sarcoma. Cancer 2008, 113:419-425.
10. Song BS, Seo J, Kim DH, Lim JS, Yoo JY, Lee JA Gemcitabine and docetaxel for the treatment of children and adolescents with recurrent or refractory osteosarcoma: Korea Cancer Center Hospital experience. Pediatr Blood Cancer 2014, 61:1376-1381.
11. Duffaud F, Egerer G, Ferrari S, Rassam H, Boecker U, Bui-Nguyen B A phase II trial of second-line pemetrexed in adults with advanced/metastatic osteosarcoma. Eur J Cancer 2012, 48:564-570.
12. Boye K, Del Prever AB, Eriksson M, et al. High-dose chemotherapy with stem cell rescue in the primary treatment of metastatic and pelvic osteosarcoma: final results of the ISG/SSG II study. Pediatr Blood Cancer 2014, 61:840-845.
13. Sampson VB, Gorlick R, Kamara D, Anders Kolb E A review of targeted therapies evaluated by the pediatric preclinical testing program for osteosarcoma. Front Oncol 2013, 3:132.
14. Schwartz GK, Tap WD, Qin LX, et al. Cixutumumab and temsirolimus for patients with bone and soft-tissue sarcoma: a multicentre, open-label, phase 2 trial. Lancet Oncol 2013, 14:371-382.
15. Pignochino Y, Grignani G, Cavalloni G, et al. Sorafenib blocks tumour growth, angiogenesis and metastatic potential in preclinical models of osteosarcoma through a mechanism potentially involving the inhibition of ERK1/2, MCL-1 and ezrin pathways. Mol Cancer 2009, 8:118-130.
16. Yang R, Piperdi S, Gorlick R Activation of the RAF/mitogen-activated protein/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase pathway mediates apoptosis induced by chelerythrine in osteosarcoma. Clin Cancer Res 2008, 14:6396-6404.
17. Kloos RT, Ringel MD, Knopp MV, et al. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol 2009, 27:1675-1684.
18. Grignani G, Palmerini E, Dileo P, et al. A phase II trial of sorafenib in relapsed and unresectable high-grade osteosarcoma after failure of standard multimodal therapy: an Italian Sarcoma Group study. Ann Oncol 2012, 23:508-516.
19. Pignochino Y, Dell'Aglio C, Basiricò M, et al. The Combination of Sorafenib and Everolimus Abrogates mTORC1 and mTORC2 upregulation in osteosarcoma preclinical models. Clin Cancer Res 2013, 19:2117-2131.
20. Amato RJ, Flaherty AL, Stepankiw M Phase I trial of everolimus plus sorafenib for patients with advanced renal cell cancer. Clin Genitourin Cancer 2012, 10:26-31.
21. Gomez-Martin C, Bustamante J, Castroagudin JF, et al. Efficacy and safety of sorafenib in combination with mammalian target of rapamycin inhibitors for recurrent hepatocellular carcinoma after liver transplantation. Liver Transpl 2012, 18:45-52.
22. Harzstark AL, Small EJ, Weinberg VK, et al. A phase 1 study of everolimus and sorafenib for metastatic clear cell renal cell carcinoma. Cancer 2011, 117:4194-4200.
23. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009, 45:228-247.
24. Tong D, Gillick L, Hendrickson FR The palliation of symptomatic osseous metastases: final results of the Study by the Radiation Therapy Oncology Group. Cancer 1982, 50:893-899.
25. Available at the URL address (last access date July 31, 2014) http://www.npcrc.org/files/news/briefpain_short.pdf.
26. Simon R Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989, 10:1-10.
27. Bagatell R, Norris R, Ingle AM, et al. Phase 1 trial of temsirolimus in combination with irinotecan and temozolomide in children, adolescents and young adults with relapsed or refractory solid tumors: a Children's Oncology Group Study. Pediatr Blood Cancer 2014, 61:833-839.
28. Luetke A, Meyers PA, Lewis I, Juergens H Osteosarcoma treatment - where do we stand? A state of the art review. Cancer Treat Rev 2014, 40:523-532.
29. Leary SE, Wozniak AW, Billups CA, et al. Survival of pediatric patients after relapsed osteosarcoma: the St. Jude Children's Research Hospital experience. Cancer 2013, 119:2645-2653.
30. Van Glabbeke M, Verweij J, Judson I, Nielsen OS Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas. Eur J Cancer 2002, 38:543-549. the EORTC Soft Tissue and Bone Sarcoma Group.
31. Ray-Coquard I, Gelderblom H, Chevreau C, et al. An open-label international multicentric phase II study of nilotinib in progressive pigmented villo-nodular synovitis (PVNS) not amenable to a conservative surgical treatment. Proc Am Soc Clin Oncol 2012, 30. abstr 10006.
32. Collins M, Wilhelm M, Conyers R, et al. Benefits and adverse events in younger versus older patients receiving neoadjuvant chemotherapy for osteosarcoma: findings from a meta-analysis. J Clin Oncol 2013, 31:2303-2312.
33. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012, 366:520-529.
34. Escudier B, Eisen T, Stadler WM, et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N Engl J Med 2007, 356:125-134. the TARGET Study Group.
35. Motzer RJ, Escudier B, Oudard S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet 2008, 372:449-456. the RECORD-1 Study Group.
36. Yao JC, Shah MH, Ito T, et al. Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 2011, 364:514-523. the RAD001 in Advanced Neuroendocrine Tumors, Third Trial (RADIANT-3) Study GroupThird Trial (RADIANT-3) Study Group.
37. Le Cesne A, Van Glabbeke M, Verweij J, et al. Absence of progression as assessed by response evaluation criteria in solid tumors predicts survival in advanced GI stromal tumors treated with imatinib mesylate: the intergroup EORTC-ISG-AGITG phase III trial. J Clin Oncol 2009, 27:3969-3974.
38. Lencioni R, Llovet JM Modified RECIST (mRECIST) assessment for hepatocellular carcinoma. Semin Liver Dis 2010, 30:52-60.
39. Choi H, Charnsangavej C, Faria SC, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol 2007, 25:1753-1759.
40. Wilhelm SM, Carter C, Tang L, et al. BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 2004, 64:7099-7109.
41. Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, González-Barón M PI3K/Akt signalling pathway and cancer. Cancer Treat Rev 2004, 30:193-204.
42. Chen D, Zhao P, Li SQ, et al. Prognostic impact of pERK in advanced hepatocellular carcinoma patients treated with sorafenib. Eur J Surg Oncol 2013, 39:974-980.
43. Adair JG The Hawthorne Effect: a reconsideration of the methodological artifact. J Appl Psychol 1984, 69:334-345.