Top

Published in:

01-12-2005 | Original Article

A phase I trial of celecoxib in combination with docetaxel and irinotecan in patients with advanced cancer

Authors: Grace K. Dy, Sumithra Mandrekar, Prema P. Peethambaram, Scott H. Okuno, Gary C. Croghan, Lorelei J. Hanson, Alfred Furth, Alex A. Adjei

Published in: Cancer Chemotherapy and Pharmacology | Issue 6/2005

Abstract

Purpose

This phase I study was conducted to determine the safety, tolerability and maximum tolerated dose of the combination of celecoxib, a selective cyclooxygenase-2 inhibitor, with docetaxel and irinotecan, in patients with advanced solid tumors.

Patients and methods

Patients with solid tumors received one of three escalating dose levels of daily celecoxib in combination with docetaxel and irinotecan administered on days 1 and 8 of an every 21-day cycle. Toxicities were graded by the National Cancer Institute Common Toxicity Criteria (NCI CTC) and recorded as maximum grade per patient for each treatment cycle.

Results

A total of 19 patients received 90 cycles of treatment through three dose levels. Dose-limiting toxicities were nausea and diarrhea. The most common treatment-related toxicities in all cycles of treatment were alopecia, fatigue, diarrhea, nausea, vomiting, anemia, anorexia, and edema.. The maximum tolerated dose was established at celecoxib 400 mg twice a day continuously, weekly docetaxel 30 mg/m² and irinotecan 50 mg/m² for 2 weeks every 21 days. Disease stabilization (five or more cycles) was documented in eight patients.

Conclusion

The combination of celecoxib with docetaxel and irinotecan did not ameliorate irinotecan-induced diarrhea. Although prolonged disease stabilization was achieved in some patients, we do not recommend combining celecoxib with docetaxel and irinotecan because of lack of activity and the side effect profile of this combination.

Smith WL, Garavito RM, DeWitt DL (1996) Prostaglandin endoperoxide H synthases (cyclooxygenases)-1 and -2. J Biol Chem 271:33157–33160PubMed

Smith WL, DeWitt DL (1995) Biochemistry of prostaglandin endoperoxide H synthase-1 and synthase-2 and their differential susceptibility to nonsteroidal anti-inflammatory drugs. Semin Nephrol 15:179–194PubMed

Kujubu DA, Fletcher BS, Varnum BC, Lim RW, Herschman HR (1991) TIS10, a phorbol ester tumor promoter-inducible mRNA from Swiss 3T3 cells, encodes a novel prostaglandin synthase/cyclooxygenase homologue. J Biol Chem 266:12866–12872PubMed

Jones DA, Carlton DP, McIntyre TM, Zimmerman GA, Prescott SM (1993) Molecular cloning of human prostaglandin endoperoxide synthase type II and demonstration of expression in response to cytokines. J Biol Chem 268:9049–9054PubMed

DuBois RN, Awad J, Morrow J, Roberts LJ, Bishop PR (1994) Regulation of eicosanoid production and mitogenesis in rat intestinal epithelial cells by transforming growth factor-alpha and phorbol ester. J Clin Invest 93:493–498PubMed

Inoue H, Yokoyama C, Hara S, Tone Y, Tanabe T (1995) Transcriptional regulation of human prostaglandin-endoperoxide synthase-2 gene by lipopolysaccharide and phorbol ester in vascular endothelial cells. Involvement of both nuclear factor for interleukin-6 expression site and cAMP response element. J Biol Chem 270:24965–24971PubMed

Subbaramaiah K, Telang N, Ramonetti JT, Araki R, DeVito B, Weksler BB, Dannenberg AJ (1996) Transcription of cyclooxygenase-2 is enhanced in transformed mammary epithelial cells. Cancer Res 56:4424–4429PubMed

Mestre JR, Subbaramaiah K, Sacks PG, Schantz SP, Tanabe T, Inoue H, Dannenberg AJ (1997) Retinoids suppress epidermal growth factor-induced transcription of cyclooxygenase-2 in human oral squamous carcinoma cells. Cancer Res 57:2890–2895PubMed

Smith WL, DeWitt DL, Garavito RM (2000) Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 69:145–182PubMed

10.

Howe LR, Subbaramaiah K, Brown AM, Dannenberg AJ (2001) Cyclooxygenase-2: a target for the prevention and treatment of breast cancer. Endocr Relat Cancer 8:97–114PubMed

11.

Dannenberg AJ, Altorki NK, Boyle JO (2001) Cyclo-oxygenase 2: a pharmacological target for the prevention of cancer. Lancet Oncol 2:544–551PubMed

12.

Dempke W, Rie C, Grothey A, Schmoll HJ (2001) Cyclooxygenase-2: a novel target for cancer chemotherapy? J Cancer Res Clin Oncol 127:411–417PubMed

13.

Kirschenbaum A, Liu X, Yao S, Levine AC (2001) The role of cyclooxygenase-2 in prostate cancer. Urology 58:127–131PubMed

14.

Prescott SM, Fitzpatrick FA (2000) Cyclooxygenase-2 and carcinogenesis. Biochim Biophys Acta 1470:M69–M78PubMed

15.

Sheng H, Shao J, Washington MK, DuBois RN (2001) Prostaglandin E2 increases growth and motility of colorectal carcinoma cells. J Biol Chem 276:18075–18081PubMed

16.

Ben-Av P, Crofford LJ, Wilder RL, Hla T (1995) Induction of vascular endothelial growth factor expression in synovial fibroblasts by prostaglandin E and interleukin-1: a potential mechanism for inflammatory angiogenesis. FEBS Lett 372:83–87PubMed

17.

Tsujii M, DuBois RN (1995) Alterations in cellular adhesion and apoptosis in epithelial cells overexpressing prostaglandin endoperoxide synthase 2. Cell 83:493–501PubMed

18.

Tsujii M, Kawano S, Tsuji S, Sawaoka H, Hori M, DuBois RN (1998). Cyclooxygenase regulates angiogenesis induced by colon cancer cells. Cell 93:705–716PubMed

19.

Sheng H, Shao J, Morrow JD, Beauchamp RD, DuBois RN (1998) Modulation of apoptosis and Bcl-2 expression by prostaglandin E2 in human colon cancer cells. Cancer Res 58:362–366PubMed

20.

Subbaramaiah K, Marmo TP, Dixon DA, Dannenberg AJ (2003) Regulation of cyclooxgenase-2 mRNA stability by taxanes: evidence for involvement of p38, MAPKAPK-2, and HuR. J Biol Chem 278(39):37637–37647PubMed

21.

Moos PJ, Muskardin DT, Fitzpatrick FA (1999) Effect of taxol and taxotere on gene expression in macrophages: induction of the prostaglandin H synthase-2 isoenzyme. J Immunol 162(1):467–473PubMed

22.

Trifan OC, Durham WF, Salazar VS (2002) Cyclooxygenase-2 inhibition with celecoxib enhances antitumor efficacy and reduces diarrhea side effect of CPT-11. Cancer Res 62:5778–5784PubMed

23.

Okishio K, Kudoh S, Hirata K, et al (1995) Schedule dependent additive effect of docetaxel and irinotecan in vitro (abstract 2252). Proc Jpn J Cancer Res 86:619

24.

Bissery MC, Couteau C, Oulid-Aissa D, et al (1997) Docetaxel in combination with irinotecan: prediction of clinical maximum tolerated dose (abstract 773). Proc Am Soc Clin Oncol 16:221a

25.

Couteau C, Risse ML, Ducreux M, Lefresne-Soulas F, Riva A, Lebecq A, Ruffie P, Rougier P, Lokiec F, Bruno R, Armand JP (2000) Phase I and pharmacokinetic study of docetaxel and irinotecan in patients with advanced solid tumors. J Clin Oncol 18(20):3545–3552PubMed

26.

Adjei AA, Klein CE, Kastrissios H, Goldberg RM, Alberts SR, Pitot HC, Sloan JA, Reid JM, Hanson LJ, Atherton P, Rubin J, Erlichman C (2000) Phase I and pharmacokinetic study of irinotecan and docetaxel in patients with advanced solid tumors: preliminary evidence of clinical activity. J Clin Oncol 18(5):1116–1123PubMed

27.

Yamamoto N, Fukuoka M, Negoro SI, Nakagawa K, Saito H, Matsui K, Kawahara M, Senba H, Takada Y, Kudoh S, Nakano T, Katakami N, Sugiura T, Hoso T, Ariyoshi Y (2004) Randomised phase II study of docetaxel/cisplatin vs docetaxel/irinotecan in advanced non-small-cell lung cancer: a West Japan Thoracic Oncology Group Study (WJTOG9803). Br J Cancer 90(1):87–92PubMed

28.

Masuda N, Negoro S, Kudoh S, Sugiura T, Nakagawa K, Saka H, Takada M, Niitani H, Fukuoka M (2000) Phase I and pharmacologic study of docetaxel and irinotecan in advanced non-small-cell lung cancer. J Clin Oncol 18(16):2996–3003PubMed

29.

Lordick F, von Schilling C, Bernhard H, Hennig M, Bredenkamp R, Peschel C (2003) Phase II trial of irinotecan plus docetaxel in cisplatin-pretreated relapsed or refractory esophageal cancer. Br J Cancer 89(4):630–633PubMed

30.

Font A, Sanchez JM, Taron M, et al (2003) Weekly regimen of irinotecan/docetaxel in previously treated non-small cell lung cancer patients and correlation with uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) polymorphism. Invest New Drugs 21(4):435–443PubMed

31.

Storer B (1989) Design and analysis of phase I clinical trials. Biometrics 45:925–937PubMedMathSciNet

32.

Goldenberg MM (1999) Celecoxib, a selective cyclooxygenase-2 inhibitor for the treatment of rheumatoid arthritis and osteoarthritis. Clin Ther 21(9):1497–1513PubMed

Title: A phase I trial of celecoxib in combination with docetaxel and irinotecan in patients with advanced cancer
Authors: Grace K. Dy
Sumithra Mandrekar
Prema P. Peethambaram
Scott H. Okuno
Gary C. Croghan
Lorelei J. Hanson
Alfred Furth
Alex A. Adjei
Publication date: 01-12-2005
Publisher: Springer-Verlag
Published in: Cancer Chemotherapy and Pharmacology / Issue 6/2005
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-004-0996-6

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Patients and methods

Results

Conclusion

Please log in to get access to this content

Other articles of this Issue 6/2005

A phase I study to determine the effect of tamoxifen on the pharmacokinetics of a single 250 mg oral dose of gefitinib (IRESSA) in healthy male volunteers

Activation and antitumor activity of CPT-11 in plasma esterase-deficient mice

Preclinical toxicity of a geldanamycin analog, 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (17-DMAG), in rats and dogs: potential clinical relevance

Methylene blue is more toxic to erythroleukemic cells than to normal peripheral blood mononuclear cells: a possible use in chemotherapy

Phase I/II trial of intraperitoneal 5-Fluorouracil with and without intravenous Vasopressin in non-resectable pancreas cancer

Signal transduction through substance P receptor in human glioblastoma cells: roles for Src and PKCδ

Keynote webinar | Spotlight on antibody–drug conjugates in cancer