Phase I and Pharmacokinetic Study of Gemcitabine Administered at Fixed-Dose Rate, Combined with Docetaxel/Melphalan/Carboplatin, with Autologous Hematopoietic Progenitor-Cell Support, in Patients with Advanced Refractory Tumors

Biology of Blood and Marrow Transplantation

Volumn 13, Issue 11, 2007, Pages 1324-1337

  Nieto, Yago ^a   Aldaz, Azucena ^b   Rifón, José ^b   Pérez Calvo, Javier ^b   Zafra, Ana ^b   Zufia, Laura ^b   Viúdez, Antonio ^b   Viteri, Santiago ^b   Aramendía, José Manuel ^b   Aristu, Javier ^b   Centeno, Carlos ^b   Moreno, Marta ^b   Sayar, Onintza ^b   Hernández, Milagros ^b  

^a UNIVERSITY OF TEXAS MD ANDERSON CANCER CENTER   (United States)

^b UNIVERSITY CLINIC OF NAVARRA   (Spain)

Author keywords

Autologous transplantation; Gemcitabine; High dose chemotherapy; Pharmacokinetics; Phase 1 trial

Indexed keywords

ACICLOVIR; AROMATASE INHIBITOR; BUSULFAN; CARBOPLATIN; CEFEPIME; CYCLOPHOSPHAMIDE; DEXAMETHASONE; DOCETAXEL; ETOPOSIDE; FLUCONAZOLE; FUROSEMIDE; GABAPENTIN; GEMCITABINE; GLUTAMINE; IFOSFAMIDE; LEVOFLOXACIN; MELPHALAN; MEROPENEM; METHYLPHENIDATE; METHYLPREDNISOLONE; MITOXANTRONE; MORPHINE; NEOSTIGMINE; PETROLATUM; PYRIDOXINE; RITUXIMAB; THIOTEPA; TRAMADOL; UNINDEXED DRUG; VANCOMYCIN;

ADOLESCENT; ADULT; AGED; ALANINE AMINOTRANSFERASE BLOOD LEVEL; AREA UNDER THE CURVE; ARTHRALGIA; ARTICLE; ASPARTATE AMINOTRANSFERASE BLOOD LEVEL; ASPIRATION PNEUMONIA; ASTHENIA; AUTOLOGOUS HEMATOPOIETIC STEM CELL TRANSPLANTATION; BLADDER METASTASIS; BONE METASTASIS; BREAST CANCER; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; CATHETER INFECTION; CHILD; CLINICAL TRIAL; CONSTIPATION; DIARRHEA; DISEASE FREE SURVIVAL; DISTRIBUTION VOLUME; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DISTRIBUTION; DRUG DOSE ESCALATION; DRUG DOSE REDUCTION; DRUG ELIMINATION; DRUG FATALITY; DRUG HALF LIFE; DRUG INFUSION; DRUG MEGADOSE; DRUG SUBSTITUTION; DRUG TOLERABILITY; DRUG WITHDRAWAL; ENGRAFTMENT SYNDROME; ENTERITIS; ENTEROCOLITIS; FEBRILE NEUTROPENIA; FEMALE; FOLLOW UP; GERM CELL TUMOR; GRAFT FAILURE; GRAFT INFECTION; HAND FOOT SYNDROME; HODGKIN DISEASE; HUMAN; HYPONATREMIA; ILEUS; INAPPROPRIATE VASOPRESSIN SECRETION; KIDNEY DISEASE; LUNG METASTASIS; MAJOR CLINICAL STUDY; MALE; MALIGNANT NEOPLASTIC DISEASE; MAXIMUM PLASMA CONCENTRATION; MEDIASTINUM METASTASIS; MUCOSA INFLAMMATION; MYALGIA; NEPHROBLASTOMA; NEUROPATHIC PAIN; NONHODGKIN LYMPHOMA; ONYCHOLYSIS; OSTEOSARCOMA; OVERALL SURVIVAL; PARALYTIC ILEUS; PERIPHERAL NEUROPATHY; PHARMACODYNAMICS; PHASE 1 CLINICAL TRIAL; RASH; RETROPERITONEAL CANCER; REVERSED PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; SEPSIS; SIDE EFFECT; SOFT TISSUE SARCOMA; STOMATITIS; TREATMENT DURATION; TREATMENT OUTCOME;

ADOLESCENT; ADULT; AGED; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CARBOPLATIN; CHILD; DEOXYCYTIDINE; DISEASE-FREE SURVIVAL; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HEMATOPOIETIC STEM CELL TRANSPLANTATION; HUMANS; MALE; MAXIMUM TOLERATED DOSE; MELPHALAN; MIDDLE AGED; NEOPLASMS; TAXOIDS; TRANSPLANTATION, AUTOLOGOUS;

EID: 35348867411     PISSN: 10838791     EISSN: 15236536     Source Type: Journal    
DOI: 10.1016/j.bbmt.2007.07.008     Document Type: Article

References (64)

1. Doroshow J.H. Pharmacological basis for high-dose chemotherapy. In: Donnall Thomas E., Blume K.G., and Forman S.J. (Eds). Hematopoietic Cell Transplantation. 2nd ed. (2004), Blackwell Science Inc, Boston, MA 103-122
2. Hanauske A.R., Degen D., Marshall M.H., Hilsenbeck S.G., Grindey G.B., and Von Hoff D.D. Activity of 2′,2′-difluorodeoxycytidine (Gemcitabine) against human tumor colony forming units. Anticancer Drugs 3 (1992) 143-146
3. Csoka K., Liliemark J., Larsson R., and Nygren P. Evaluation of the cytotoxic activity of gemcitabine in primary cultures of tumor cells from patients with hematologic or solid tumors. Semin Oncol 22 Suppl 11 (1995) 47-53
4. Braakhuis B.J., van Haperen V.W., Boven E., Veerman G., and Peters G.J. Schedule-dependent antitumor effect of gemcitabine in in vivo model system. Semin Oncol 22 Suppl 11 (1995) 42-46
5. Veerman G., van Haperen V.W.T., Vermorken J., et al. Antitumor activity of prolonged as compared with bolus administration of 2′,2′-difluorodeoxycytidine in vivo against murine colon tumors. Cancer Chemother Pharmacol 38 (1996) 335-342
6. Plunkett W., Huang P., Xu Y.-Z., Heinemann V., Grunewald R., and Gandhi V. Gemcitabine: metabolism, mechanisms of action, and self-potentiation. Semin Oncol 22 Suppl 11 (1995) 3-10
7. Grunewald R., Abbruzzese J.L., Tarassoff P., and Plunkett W. Saturation of 2′,2′-difluorodeoxycytidine 5′-triphosphate accumulation by mononuclear cells during a phase I trial of gemcitabine. Cancer Chemother Pharmacol 27 (1991) 258-262
8. Grunewald R., Kantarjian H., Keating M.J., Abbruzzese J., Tarassoff P., and Plunkett W. Pharmacologically directed design of the dose rate and schedule of 2′,2′-difluorodeoxycytidine (Gemcitabine) administration in leukemia. Cancer Res 50 (1990) 6823-6826
9. Grunewald R., Kantarjian H., Du M., Faucher K., Tarassoff P., and Plunkett W. Gemcitabine in leukemia: a phase I clinical, plasma, and cellular pharmacology study. J Clin Oncol 10 (1992) 406-413
10. Gandhi V., Plunkett W., Du M., Ayres M., and Estey E.H. Prolonged infusion of gemcitabine: clinical and pharmacodynamic studies during a phase I trial in relapsed acute myelogenous leukemia. J Clin Oncol 20 (2002) 665-673
11. Tempero M., Plunkett W., Ruiz Van Haperen V., et al. Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 21 (2003) 3402-3408
12. Soo R.A., Wang L.Z., Tham L.S., et al. A multicenter randomized phase II study of carboplatin in combination with gemcitabine at standard rate or fixed dose rate infusion in patients with advanced stage non-small-cell lung cancer. Ann Oncol 17 (2006) 1128-1133
13. Nieto Y., Shpall E.J., Bearman S.I., et al. Phase I and pharmacokinetic study of docetaxel combined with melphalan and carboplatin, with autologous hematopoietic progenitor cell support, in patients with advanced refractory malignancies. Biol Blood Marrow Transplant 11 (2005) 297-306
14. Van Moorsel C.J., Pinedo H.M., Veerman G., et al. Mechanisms of synergism between cisplatin and gemcitabine in ovarian and non-small-cell lung cancer cell lines. Br J Cancer 80 (1999) 981-990
15. Bergman A.M., Ruiz van Haperen V.W., Veerman G., Kuiper C.M., and Peters G.J. Synergistic interaction between cisplatin and gemcitabine in vitro. Clin Cancer Res 2 (1996) 521-530
16. Leu K.M., Ostruszka L.J., Shewach D., et al. Laboratory and clinical evidence of synergistic cytotoxicity of sequential treatment with gemcitabine followed by docetaxel in the treatment of sarcoma. J Clin Oncol 22 (2004) 1706-1712
17. Alexopoulos A., Tryfonopoulos D., Karamouzis M.V., et al. Evidence for in vivo synergism between docetaxel and gemcitabine in patients with metastatic breast cancer. Ann Oncol 15 (2004) 95-99
18. Maki R.G., Wathen J.K., Patel S.R., et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas. J Clin Oncol 25 (2007) 2755-2763
19. Cockroft D.W., and Gault M.H. Prediction of creatinine clearance from serum creatinine. Nephron 16 (1976) 31-41
20. Calvert A.H., Newell D.R., Gumbrell L.A., et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol 7 (1989) 1748-1756
21. Dumontet C., Sonnet A., Bastion Y., Salles G., Espinouse D., and Coiffier B. Prevention of high dose L-PAM induced mucositis by cryotherapy. Bone Marrow Transplant 14 (1994) 492-494
22. Meloni G., Capria S., Proia A., Trisolini S.M., and Mandelli F. Ice pops to prevent melphalan-induced stomatitis. Lancet 347 (1996) 1691-1692
23. Lilleby K., Garcia P., Gooley T., et al. A prospective, randomized study of cryotherapy during administration of high-dose melphalan to decrease the severity and duration of oral mucositis in patients with multiple myeloma undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 37 (2006) 1031-1035
24. Anderson P.M., Schroeder G., and Skubitz K.M. Oral glutamine reduces the duration and severity of stomatitis after cytotoxic cancer chemotherapy. Cancer 83 (1998) 1433-1439
25. Anderson P.M., Ramsay N.K.C., Shu X.O., et al. Effect of low-dose oral glutamine on painful stomatitis during bone marrow transplantation. Bone Marrow Transplant 22 (1998) 339-344
26. Cockerham M.B., Weinberger B.B., and Lerchie S.B. Oral glutamine for the prevention of oral mucositis associated with high-dose paclitaxel and melphalan for autologous bone marrow transplantation. Ann Pharmacother 34 (2000) 300-303
27. Mossad S., Kalaycio M., Sobecks R., et al. Steroids prevent engraftment syndrome after autologous hematopoietic stem cell transplantation without increasing the risk of infection. Bone Marrow Transplant 35 (2005) 375-381
28. Ponec R.J., Saunders M.D., and Kimmey M.B. Neostigmine for the treatment of acute colonic pseudo-obstruction. N Engl J Med 341 (1999) 137-141
29. Bruera E., Driver L., Barnes E.A., et al. Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: a preliminary report. J Clin Oncol 21 (2003) 4439-4443
30. Kroep J.R., Giaccone G., Voorn D.A., et al. Gemcitabine and paclitaxel: pharmacokinetic and pharmacodynamic interactions in patients with non-small-cell lung cancer. J Clin Oncol 17 (1999) 2190-2197
31. Zufia L., Aldaz A., Aramendía J.M., Arrobase J., and Giráldez J. Determination of docetaxel and paclitaxel in human plasma by high-performance liquid chromatography. Ther Drug Monit 28 (2006) 199-205
32. http://ctep.cancer.gov/forms/CTCv20_4-30-992.pdf. Accessed August 8, 2007.
33. Therasse P., Arbuck S.G., Eisenhauer E.A., et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 92 (2000) 205-216
34. Cheson B.D., Horning S.J., Coiffier B., et al. Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol 17 (1999) 1244-1253
35. Baker S.K., Zhao M., Lee C.K.K., et al. Comparative pharmacokinetics of weekly and every-three-weeks docetaxel. Clin Cancer Res 10 (2004) 1976-1983
36. Harvey V.H., Mouridsen H., Semiglazov V., et al. Phase III trial comparing three doses of docetaxel for second-line treatment of advanced breast cancer. J Clin Oncol 24 (2006) 4963-4970
37. Bruno R., Hille D., Riva A., et al. Population pharmacokinetics/pharmacodynamics of docetaxel in phase II studies in patients with cancer. J Clin Oncol 16 (1998) 187-196
38. Gonçalves A., Viret F., Ciccolini J., et al. Phase I and pharmacokinetic study of escalating doses of docetaxel administered with granulocyte colony-stimulating factor support in adult advanced tumors. Clin Cancer Res 9 (2003) 102-108
39. Wang H., Li M., Rinehart J.J., and Zhang R. Pretreatment with dexamethasone increases antitumor activity of carboplatin and gemcitabine in mice bearing human cancer xenografts: in vivo activity, pharmacokinetics, and clinical implications for cancer chemotherapy. Clin Cancer Res 10 (2004) 1633-1644
40. Touroutoglou N., Gravel D., Raber M.N., Plunkett W., and Abbruzzese J.L. Clinical results of a pharmacodynamically-based strategy for higher dosing of gemcitabine in patients with solid tumors. Ann Oncol 9 (1998) 1003-1008
41. Brand R., Capadano M., and Tempero M. A phase I trial of weekly gemcitabine administered as a prolonged infusion in patients with pancreatic cancer and other solid tumors. Invest New Drugs 15 (1997) 331-341
42. Bass A.J., Gockerman J.P., Hammett E., et al. Phase I evaluation of prolonged-infusion gemcitabine with irinotecan for relapsed or refractory leukemia or lymphoma. J Clin Oncol 20 (2002) 2995-3000
43. Rizzieri D.A., Bass A.J., Rosner G.L., et al. Phase I evaluation of prolonged-infusion gemcitabine with mitoxantrone for relapsed or refractory acute leukemia. J Clin Oncol 20 (2002) 674-679
44. Rizzieri D.A., Ibom V.K., Moore J.O., et al. Phase I evaluation of prolonged-infusion gemcitabine with fludarabine for relapsed or refractory acute myelogenous leukemia. Clin Cancer Res 9 (2003) 663-668
45. Bengala C., Guarneri V., Giovannetti E., et al. Prolonged fixed dose rate infusion of gemcitabine with autologous haemopoietic support in advanced pancreatic adenocarcinoma. Br J Cancer 93 (2005) 35-40
46. Crump M., Baetz T., Couban S., et al. Gemcitabine, dexamethasone, and cisplatin in patients with recurrent or refractory aggressive histology B-cell non-Hodgkin lymphoma: a Phase II study by the National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG). Cancer 101 (2004) 1835-1842
47. Müller-Beissenhirtz H., Kasper C., Nückel H., and Dührsen U. Gemcitabine, vinorelbine and prednisone for refractory or relapsed aggressive lymphoma, results of a phase II single center study. Ann Hematol 84 (2005) 796-801
48. Di Renzo N., Brugiatelli M., Montanini A., et al. Vinorelbine, gemcitabine, procarbazine and prednisone (ViGePP) as salvage therapy in relapsed or refractory aggressive non-Hodgkin's lymphoma (NHL): results of a phase II study conducted by the Gruppo Italiano per lo Studio dei Linfomi. Leuk Lymphoma 47 (2006) 473-479
49. Kuruvilla J., Nagy T., Pintilie M., Tsang R., Keating A., and Crump M. Similar response rates and superior early progression-free survival with gemcitabine, dexamethasone, and cisplatin salvage therapy compared with carmustine, etoposide, cytarabine, and melphalan salvage therapy prior to autologous stem cell transplantation for recurrent or refractory Hodgkin lymphoma. Cancer 106 (2006) 353-360
50. Santoro A., Magagnoli M., Spina M., et al. Ifosfamide, gemci-tabine, and vinorelbine: a new induction regimen for refractory and relapsed Hodgkin's lymphoma. Haematologica 92 (2007) 35-41
51. Einhorn L.H., Brames M.J., Juliar B., and Williams S.D. Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after progression following high-dose chemotherapy with tandem transplant. J Clin Oncol 25 (2007) 513-516
52. De Giorgi U., Rosti G., Aieta M., et al. Phase II study of oxaliplatin and gemcitabine salvage chemotherapy in patients with cisplatin-refractory nonseminomatous germ cell tumor. Eur Urol 50 (2006) 1032-1038
53. Kollmannsberger C., Beyer J., Liersch R., et al. Combination chemotherapy with gemcitabine plus oxaliplatin in patients with intensively pretreated or refractory germ cell cancer: a study of the German Testicular Cancer Study Group. J Clin Oncol 22 (2004) 108-114
54. Crump M., Gluck S., Stewart D., et al. A randomized trial of high-dose chemotherapy (HDC) with autologous peripheral blood stem cell support (AHPCT) compared to standard chemotherapy in women with metastatic breast cancer: a National Cancer Institute of Canada (NCIC) Clinical Trials Group study. Proc Am Soc Clin Oncol 20 (2001) [abstract 21]
55. Biron P., Durand M., Roché H., et al. High dose thiotepa (TTP), cyclophosphamide (CPM) and stem cell transplantation after 4 FEC 100 compared with 4 FEC alone allowed a better disease free survival but the same overall survival in first line chemotherapy for metastatic breast cancer. Results of the PEGASE 03 French protocol. Proc Am Soc Clin Oncol 21 (2002) Abstract 42
56. Crown J., Perey L., Lind M., et al. Superiority of tandem high-dose chemotherapy (HDC) versus optimized conventionally-dosed chemotherapy (CDC) in patients (pts) with metastatic breast cancer (MBC): the International Breast Cancer Dose Intensity Study (IBDIS 1). Proc Am Soc Clin Oncol 22 (2003) [abstract 23]
57. Lotz J.P., Cure H., Asselain B., et al. High-dose chemotherapy with haematopoietic stem cell transplantation for metastatic breast cancer patients: final results of the French multicentric randomised CMA/PEGASE 04 protocol. Eur J Cancer 41 (2005) 71-80
58. Vredenburgh J., Coniglio D., Broadwater G., et al. Consolidation with high-dose combination alkylating agents with bone marrow transplantation significantly improves disease-free survival in hormone-insensitive metastatic breast cancer in complete remission compared with intensive standard-dose chemotherapy alone. Biol Blood Marrow Transplant 12 (2006) 195-203
59. Vredenburgh J., Madan B., Broadwater G., et al. A randomized phase III comparative trial of immediate consolidation with high-dose chemotherapy and autologous peripheral blood progenitor cell support compared to observation with delayed consolidation in women with metastatic breast cancer and only bone metastases following intensive induction chemotherapy. Bone Marrow Transplant 37 (2006) 1009-1015
60. Farquhar C., Marjoribanks J., Basser R., et al. High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with metastatic breast cancer. Cochrane Database Syst Rev 3 (2005) CD003142
61. Pegram M.D., Lopez A., Konecny G., and Slamon D.J. Trastuzumab and chemotherapeutics: drug interactions and synergies. Semin Oncol 27 Suppl 11 (2000) 21-25
62. Tong R.T., Boucher Y., Kozin S.V., et al. Vascular normalization by vascular endothelial growth factor receptor 2 blockade induces a pressure gradient across the vasculature and improves drug penetration in tumors. Cancer Res 64 (2004) 3731-3736
63. Kindler H.L., Friberg G., Singh D.A., et al. Phase II trial of bevacizumab plus gemcitabine in patients with advanced pancreatic cancer. J Clin Oncol 23 (2005) 8033-8040
64. Sweeney C.J., Miller K.D., Sissons S.E., et al. The antiangiogenic property of docetaxel is synergistic with a recombinant humanized monoclonal antibody against vascular endothelial growth factor or 2-methoxyestradiol but antagonized by endothelial growth factors. Cancer Res 61 (2001) 3369-3372