nach oben

Erschienen in:

01.10.2009 | PHASE I STUDIES

Phase I trial of docetaxel given every 3 weeks and daily lenalidomide in patients with advanced solid tumors

verfasst von: Sharon L. Sanborn, Joseph Gibbons, Smitha Krishnamurthi, Joanna M. Brell, Afshin Dowlati, Joseph A. Bokar, Charles Nock, Nancy Horvath, Jacob Bako, Scot C. Remick, Matthew M. Cooney

Erschienen in: Investigational New Drugs | Ausgabe 5/2009

Einloggen, um Zugang zu erhalten

Summary

Purpose Cytotoxic and anti-angiogenic drugs are efficacious in malignancies. This trial was undertaken to evaluate the toxicity of a novel regimen combining docetaxel and lenalidomide. Patients and methods Patients with advanced solid tumors were eligible. Docetaxel was administered on day 1, and lenalidomide was given on days 1–14 of each 21-day cycle. Since significant myelosuppression occurred, pegfilgrastim was added on day 2. Dose limiting toxicity (DLT) was defined as ≥grade 3 non-hematologic toxicity, grade 4 neutropenia with fever, or grade 4 anemia or thrombocytopenia. Results Thirty-three patients were enrolled. DLTs included neutropenia, nausea/vomiting, and dyspnea. Of the evaluable patients, 69% had stable disease, and 3% had partial response. Conclusions This regimen was well tolerated and provided stable disease in the majority of advanced cancer patients. The recommended phase II dosing is docetaxel 75 mg/m² on day 1, lenalidomide 25 mg on days 1–14, and pegfilgrastim 6 mg on day 2, given every 3 weeks.

Folkman J (1971) Tumor angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186PubMed

Harris AL (1997) Antiangiogenesis for cancer therapy. Lancet 349:13–15. doi:10.1016/S0140-6736(97)90014-3 CrossRef

Jain RK (2005) Antiangiogenic therapy for cancer: current and emerging concepts. Oncology 19:7–16 Williston ParkPubMed

Kerbel RS (1991) Inhibition of tumor angiogenesis as a strategy to circumvent acquired resistance to anti-cancer therapeutic agents. Bioessays 13:31–36. doi:10.1002/bies.950130106 PubMedCrossRef

Klement G, Baruchel S, Rak J et al (2000) Continuous low-dose therapy with vinblastine and VEGF receptor-2 antibody induces sustained tumor regression without overt toxicity. J Clin Invest 105:R15–R24. doi:10.1172/JCI8829 PubMedCrossRef

Browder T, Butterfield CE, Kraling BM et al (2000) Antiangiogenic scheduling of chemotherapy improves efficacy against experimental drug-resistant cancer. Cancer Res 60:1878–1886PubMed

Folkman J (1995) Clinical applications of research on angiogenesis. N Engl J Med 333:1757–1763. doi:10.1056/NEJM199512283332608 PubMedCrossRef

Kerbel RS (2000) Tumor angiogenesis: past, present and the near future. Carcinogenesis 21:505–515. doi:10.1093/carcin/21.3.505 PubMedCrossRef

Scappaticci FA (2002) Mechanisms and future directions for angiogenesis-based cancer therapies. J Clin Oncol 20:3906–3927. doi:10.1200/JCO.2002.01.033 PubMedCrossRef

10.

Hudis CA (2005) Clinical implications of antiangiogenic therapies. Oncology 19:26–31 Williston ParkPubMed

11.

Teicher BA (1999) Combination of antiangiogenic agents with standard cytotoxic therapies in therapeutic regimens. Clin Cancer Res 5:3878s–3879s

12.

Sanborn SL, Cooney MM, Dowlati A et al (2008) Phase I trial of docetaxel and thalidomide: a regimen based on metronomic therapeutic principles. Invest New Drugs 26:355–362. doi:10.1007/s10637-008-9137-0 PubMedCrossRef

13.

Dredge K, Marriott JB, Macdonald CD et al (2002) Novel thalidomide analogues display anti-angiogenic activity independently of immunomodulatory effects. Br J Cancer 87:1166–1172. doi:10.1038/sj.bjc.6600607 PubMedCrossRef

14.

Richardson PG, Schlossman RL, Weller E et al (2002) Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma. Blood 100:3063–3067. doi:10.1182/blood-2002-03-0996 PubMedCrossRef

15.

Belotti D, Vergani V, Drudis T et al (1996) The microtubule-affecting drug paclitaxel has antiangiogenic activity. Clin Cancer Res 2:1843–1849PubMed

16.

Hotchkiss KA, Ashton AW, Sparano J et al (2000) Inhibition of endothelial cell function by docetaxel (Taxotere). Proc Am Assoc Cancer Res 41:647

17.

Sweeney CJ, Miller KD, Sissons SE et al (2001) 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 61:3369–3372PubMed

18.

Sweeney CJ, Sissions SE, Nozaki S et al (2000) Overcoming resistance to the anti-angiogenic properties of docetaxel induced by endothelial cell stimulation. Proc Am Assoc Cancer Res 41:647

19.

Therasse P, Arbuck SG, Eisenhauer EA et al (2000) 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 92:205–216. doi:10.1093/jnci/92.3.205 PubMedCrossRef

20.

Kerbel RS (1997) A cancer therapy resistant to resistance. Nature 390:335–336. doi:10.1038/36978 PubMedCrossRef

21.

Bello L, Carrabba G, Giussani C et al (2001) Low-dose chemotherapy combined with an antiangiogenic drug reduces human glioma growth in vivo. Cancer Res 61:7501–7506PubMed

22.

Klement G, Huang P, Mayer B et al (2002) Differences in therapeutic indexes of combination metronomic chemotherapy and an anti-VEGFR-2 antibody in multidrug-resistant human breast cancer xenografts. Clin Cancer Res 8:221–232PubMed

23.

Man S, Bocci G, Francia G et al (2002) Antitumor effects in mice of low-dose (metronomic) cyclophosphamide administered continuously through the drinking water. Cancer Res 62:2731–2735PubMed

24.

Pietras K, Hanahan D (2005) A multitargeted, metronomic, and maximum-tolerated dose “chemo-switch” regimen is antiangiogenic, producing objective responses and survival benefit in a mouse model of cancer. J Clin Oncol 23:939–952. doi:10.1200/JCO.2005.07.093 PubMedCrossRef

25.

Takahashi N, Haba A, Matsuno F et al (2001) Antiangiogenic therapy of established tumors in human skin/severe combined immunodeficiency mouse chimeras by anti-endoglin (CD105) monoclonal antibodies, and synergy between anti-endoglin antibody and cyclophosphamide. Cancer Res 61:7846–7854PubMed

26.

Teicher BA, Sotomayor EA, Huang ZD (1992) Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and metastatic disease. Cancer Res 52:6702–6704PubMed

27.

Vogt T, Hafner C, Bross K et al (2003) Antiangiogenetic therapy with pioglitazone, rofecoxib, and metronomic trofosfamide in patients with advanced malignant vascular tumors. Cancer 98:2251–2256. doi:10.1002/cncr.11775 PubMedCrossRef

28.

Spieth K, Kaufmann R, Gille J (2003) Metronomic oral low-dose treosulfan chemotherapy combined with cyclooxygenase-2 inhibitor in pre-treated advanced melanoma: a pilot study. Cancer Chemother Pharmacol 52:377–382. doi:10.1007/s00280-003-0678-9 PubMedCrossRef

29.

Hafner C, Reichle A, Vogt T (2005) New indications for established drugs: combined tumor-stroma-targeted cancer therapy with PPARγ agonists, COX-2 inhibitors, mTOR antagonists and metronomic chemotherapy. Curr Cancer Drug Targets 5:393–419. doi:10.2174/1568009054863591 PubMedCrossRef

30.

McDermott DF, Cho DC, Merchan JR et al (2006) A phase II pilot trial of low dose, continuous infusion, or “metronomic”, paclitaxel and oral celecoxib in patients with metastatic melanoma. Proc Am Assoc Cancer Res 24:8010

31.

Young SD, Whissell M, Noble JC et al (2006) Phase II clinical trial results involving treatment with low-dose daily oral cyclophosphamide, weekly vinblastine, and rofecoxib in patients with advanced solid tumors. Clin Cancer Res 12:3092–3098. doi:10.1158/1078-0432.CCR-05-2255 PubMedCrossRef

32.

Miller K, Wang M, Gralow J et al (2007) Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N Engl J Med 357:2666–2676. doi:10.1056/NEJMoa072113 PubMedCrossRef

33.

Hurwitz H, Fehrenbacher L, Novotny W et al (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350:2335–2342. doi:10.1056/NEJMoa032691 PubMedCrossRef

34.

Sandler A, Gray R, Perry MC et al (2006) Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med 355:2542–2550. doi:10.1056/NEJMoa061884 PubMedCrossRef

35.

Bartlett JB, Michael A, Clarke IA et al (2004) Phase I study to determine the safety, tolerability and immunostimulatory activity of thalidomide analogue CC-5013 in patients with metastatic malignant melanoma and other advanced cancers. Br J Cancer 90:955–961. doi:10.1038/sj.bjc.6601579 PubMedCrossRef

36.

Dredge K, Horsfall R, Robinson SP et al (2005) Orally administered lenalidomide (CC-5013) in anti-angiogenic in vivo and inhibits endothelial cell migration and Akt phosphorylation in vitro. Microvasc Res 69:56–63. doi:10.1016/j.mvr.2005.01.002 PubMedCrossRef

37.

List A (2007) Lenalidomide—the phoenix rises. N Engl J Med 357:2183–2186. doi:10.1056/NEJMe078203 PubMedCrossRef

38.

Rajkumar SV, Hayman SR, Lacy MQ et al (2005) Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 106:4050–4053. doi:10.1182/blood-2005-07-2817 PubMedCrossRef

39.

Dimopoulos M, Spencer A, Attal M et al (2007) Lenalidomide plus dexamethasone for relapsed or refractory multiple myeloma. N Engl J Med 357:2123–2132. doi:10.1056/NEJMoa070594 PubMedCrossRef

40.

Weber DM, Chen C, Niesvizky R et al (2007) Lenalidomide plus dexamethasone for relapsed multiple myeloma in North America. N Engl J Med 357:2133–2142. doi:10.1056/NEJMoa070596 PubMedCrossRef

41.

List A, Dewald G, Bennett J et al (2006) Lenalidomide in the myelodysplastic syndrome with chromosome 5q deletion. N Engl J Med 355:1456–1465. doi:10.1056/NEJMoa061292 PubMedCrossRef

42.

List A, Kurtin S, Roe DJ et al (2005) Efficacy of lenalidomide in myelodysplastic syndromes. N Engl J Med 352:549–557. doi:10.1056/NEJMoa041668 PubMedCrossRef

43.

Witzig TE, Vose J, Pietronigro D et al (2007) Preliminary results from a phase II study of lenalidomide oral monotherapy in relapsed/refractory indolent non-Hodgkin lymphoma. Proc Am Assoc Cancer Res 25:8066

44.

Wiernik PH, Lossos IS, Tuscano J et al (2007) Preliminary results from a phase II study of lenalidomide oral monotherapy in relapsed/refractory aggressive non-Hodgkin’s lymphoma. Proc Am Assoc Cancer Res 25:8052

45.

Bedikian AY, Kim K, Papadopoulos N et al (2007) Preliminary results from a phase I/II study of the combination of lenalidomide and DTIC in patients with metastatic malignant melanoma previously untreated with systemic chemotherapy. Proc Am Assoc Cancer Res 25:8533

46.

Zhang MM, Chan JK, Husain A et al (2007) Safety and efficacy of lenalidomide (Revlimid) in recurrent ovarian and primary peritoneal carcinoma. Gynecol Oncol 105:194–198. doi:10.1016/j.ygyno.2006.11.026 PubMedCrossRef

47.

Dreicer R, Garcia J, Smith S et al (2007) Phase I/II trial of GM-CSF and lenalidomide in patients with hormone refractory prostate cancer (HRPC). Proc Am Assoc Cancer Res 25:15515

48.

Choueiri TK, Dreicer R, Rini BI et al (2006) Phase II study of lenalidomide in patients with metastatic renal cell carcinoma. Cancer 107:2609–2616. doi:10.1002/cncr.22290 PubMedCrossRef

49.

Patel PH, Kondagunta GV, Schwartz L et al (2008) Phase II trial of lenalidomide in patients with metastatic renal cell carcinoma. Invest New Drugs 26:273–276. doi:10.1007/s10637-007-9107-y PubMedCrossRef

50.

Shammo JM, Kassar M, Robin I et al (2007) A case report of sarcoma regression in a patient with MDS treated with lenalidomide. Proc Am Assoc Cancer Res 25:20535

51.

Tohnya TM, Gulley J, Arlene P et al (2006) Phase I study of lenalidomide, a novel thalidomide analog, in patients with refractory metastatic cancer. Proc Am Assoc Cancer Res 24:13038

52.

Sharma RA, Steward WP, Daines CA et al (2006) Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide: phase I clinical trial of three dosing schedules in patients with solid malignancies. Eur J Cancer 42:2318–2325. doi:10.1016/j.ejca.2006.05.018 PubMedCrossRef

53.

Moss RA, Mohile SG, Shelton G et al (2007) A phase I open-label study using lenalidomide and docetaxel in androgen independent prostate cancer (AIPC). ASCO Prostate Cancer Symposium 89

54.

Kalmadi S, Davis M, Dowlati A et al (2007) Phase I trial of three-weekly docetaxel, carboplatin and oral lenalidomide (Revlimid®) in patients with advanced solid tumors. Invest New Drugs 25:211–216. doi:10.1007/s10637-006-9025-4 PubMedCrossRef

55.

Lyman GH, Khorana AA, Falanga A et al (2007) American society of clinical oncology guideline: recommendations for venous thromboembolism prophylaxis and treatment in patients with cancer. J Clin Oncol 25:5490–5505. doi:10.1200/JCO.2007.14.1283 PubMedCrossRef

56.

Dahut WL, Gulley JL, Arlen PM et al (2004) Randomized phase II trial of docetaxel plus thalidomide in androgen-independent prostate cancer. J Clin Oncol 22:2532–2539. doi:10.1200/JCO.2004.05.074 PubMedCrossRef

57.

Zangari M, Anaissie E, Barlogie B et al (2001) Increased risk of deep-vein thrombosis in patients with multiple myeloma receiving thalidomide and chemotherapy. Blood 98:1614–1615. doi:10.1182/blood.V98.5.1614 PubMedCrossRef

58.

Angelotta C, Lurie AJ, Lurie AJ et al (2006) Black box warning on lenalidomide-associated venous thromboembolism (VTE) in off-label setting: A preemptive and unusual safety initiative. Proc Am Assoc Cancer Res 24:6074

59.

Bennett CL, Angelotta C, Yarnold PR et al (2006) Thalidomide- and lenalidomide-associated thromboembolism among patients with cancer. JAMA 296:2558–2560. doi:10.1001/jama.296.21.2558-c PubMedCrossRef

60.

Horstmann E, McCabe MS, Grochow L et al (2005) Risks and benefits of phase 1 oncology trials, 1991 through 2002. N Engl J Med 352:895–904. doi:10.1056/NEJMsa042220 PubMedCrossRef

Titel: Phase I trial of docetaxel given every 3 weeks and daily lenalidomide in patients with advanced solid tumors
verfasst von: Sharon L. Sanborn
Joseph Gibbons
Smitha Krishnamurthi
Joanna M. Brell
Afshin Dowlati
Joseph A. Bokar
Charles Nock
Nancy Horvath
Jacob Bako
Scot C. Remick
Matthew M. Cooney
Publikationsdatum: 01.10.2009
Verlag: Springer US
Erschienen in: Investigational New Drugs / Ausgabe 5/2009
Print ISSN: 0167-6997
Elektronische ISSN: 1573-0646
DOI: https://doi.org/10.1007/s10637-008-9200-x

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Phase I trial of docetaxel given every 3 weeks and daily lenalidomide in patients with advanced solid tumors

Summary

Neu im Fachgebiet Onkologie

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

Update Onkologie

Die Highlights vom Kongress des American College of Cardiology 2024

Springer Medizin

Summary

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2009

Phase II trial of romidepsin (NSC-630176) in previously treated colorectal cancer patients with advanced disease: a Southwest Oncology Group study (S0336)

Artemisinin reduces human melanoma cell migration by down-regulating αVβ3 integrin and reducing metalloproteinase 2 production

Phase III trial of standard versus dose-intensified doxorubicin, ifosfamide and dacarbazine (MAID) in the first-line treatment of metastatic and locally advanced soft tissue sarcoma

Amino acetate functionalized Schiff base organotin(IV) complexes as anticancer drugs: synthesis, structural characterization, and in vitro cytotoxicity studies

Extracts of marine sponge Polymastia janeirensis induce oxidative cell death through a caspase-9 apoptotic pathway in human U138MG glioma cell line

Characterization of the cytotoxic activity of the indoloquinoline alkaloid cryptolepine in human tumour cell lines and primary cultures of tumour cells from patients

Neu im Fachgebiet Onkologie

Alphablocker schützt vor Miktionsproblemen nach der Biopsie

Antikörper-Wirkstoff-Konjugat hält solide Tumoren in Schach

Mammakarzinom: Senken Statine das krebsbedingte Sterberisiko?

Labor, CT-Anthropometrie zeigen Risiko für Pankreaskrebs

Update Onkologie