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01.07.2007 | Clinical Trial Report

Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors: phase IB trial

verfasst von: Tomislav Dragovich, Mark Huberman, Daniel D. Von Hoff, Eric K. Rowinsky, Paul Nadler, Debra Wood, Marta Hamilton, George Hage, Julie Wolf, Amita Patnaik

Erschienen in: Cancer Chemotherapy and Pharmacology | Ausgabe 2/2007

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Abstract

Purpose

The purpose of this phase IB trial was to evaluate the tolerability, pharmacokinetics and preliminary evidence of antitumor activity of erlotinib plus gemcitabine in patients with pancreatic cancer and other solid tumors.

Patients and methods

Patients included those with advanced pancreatic adenocarcinoma or other malignancies potentially responsive to gemcitabine. In the escalating phase of the trial, patients were enrolled in sequential cohorts using 100 or 150 mg oral daily dosing of erlotinib. Gemcitabine dose was 1,000 mg/m² weekly ×7 (first cycle), then weekly ×3, every 4 weeks.

Results

Twenty-six patients completed at least one course on study. In Cohort IA, at the 100 mg/day dose of erlotinib, three patients have developed grade 3 transaminase elevations. After stricter inclusion criteria were adopted (Cohort IB), no additional events of grade 3 transaminase elevations were observed and the dose of erlotinib was escalated to 150 mg/day (Cohorts IB and IIB) without reaching dose-limiting toxicities. The most common toxicities included diarrhea, skin rash, fatigue and neutropenia. The pharmacokinetic analyses did not reveal any significant interactions between erlotinib and gemcitabine. Objective responses were seen in two patients: cholangiocarcinoma and pancreatic cancer. Patients with unresectable or metastatic pancreatic cancer (n = 15) had a median progression-free survival of 289 days, the estimated overall survival of 389 days (12.5 months), and a 1-year survival rate of 51%.

Conclusion

The 150 mg/day dose of erlotinib can be safely administered in combination with standard dose gemcitabine in selected patients with pancreatic cancer and other advanced solid tumors. Promising antitumor activity has been observed in patients with pancreatic cancer.

Jemal A, Siegel R, Ward E et al (2006) Cancer statistics, 2006. CA Cancer J Clin 56:106–130PubMedCrossRef

Burris HA 3rd, Moore MJ, Andersen J et al (1997) Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol 15:2403–2413PubMed

Rothenberg ML, Moore MJ, Cripps MC et al (1996) A phase II trial of gemcitabine in patients with 5-FU-refractory pancreas cancer. Ann Oncol 7:347–353PubMed

Tempero M, Plunkett W, Ruiz Van Haperen V et al (2003) Randomized phase II comparison of dose-intense gemcitabine: thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 21:3402–3408PubMedCrossRef

O’Rielly E, Abou-Alfa GK, Letourneau R et al (2004) A randomized phase III trial of DX-8951f (exatecan mesylate; DX) and gemcitabine (GEM) vs gemcitabine alone in advanced pancreatic cancer. ASCO Annu Meet Proc 22:315s

Berlin JD, Catalano P, Thomas JP et al (2002) Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol 20:3270–3275PubMedCrossRef

Rocha Lima C, Rotche R, Jeffery M (2003) A randomized phase 3 study comparing efficacy and safety of gemcitabine (GEM) and irinotecan (I), to GEM alone in patients (pts) with locally advanced or metastatic pancreatic cancer who have not received prior systemic therapy. ASCO Annu Meet Proc 22:251

Louvet C, Labianca R, Hammel P (2004) GemOx (gemcitabine + oxaliplatin) versus Gem (gemcitabine) in non resectable pancreatic adenocarcinoma: final results of the GERCOR/GISCAD intergroup phase III. ASCO Annu Meet Proc 22:315s

Heinemann V, Quietzsch D, Fieseler F et al (2003) A phase III trial comparing gemcitabine plus cisplatin vs. gemcitabine alone in advanced pancreatic carcinoma. Proc ASCO 22:250

10.

Kindler H, Friberg G, Stadler W (2004) Bevacizumab (B) plus gemcitabine (G) in patients (pts) with advanced pancreatic cancer (PC): updated results of a multi-center phase II trial. ASCO Annu Meet Proc 22:315s

11.

Xiong HQ, Rosenberg A, LoBuglio A et al (2004) Cetuximab, a monoclonal antibody targeting the epidermal growth factor receptor, in combination with gemcitabine for advanced pancreatic cancer: a multicenter phase II trial. J Clin Oncol 22:2610–2616PubMedCrossRef

12.

Mendelsohn J (2002) Targeting the epidermal growth factor receptor for cancer therapy. J Clin Oncol 20:1S–13SPubMed

13.

Salomon DS, Brandt R, Ciardiello F et al (1995) Epidermal growth factor-related peptides and their receptors in human malignancies. Crit Rev Oncol Hematol 19:183–232PubMed

14.

Xiong HQ, Abbruzzese JL (2002) Epidermal growth factor receptor-targeted therapy for pancreatic cancer. Semin Oncol 29:31–37PubMed

15.

Hidalgo M (2003) Erlotinib: preclinical investigations. Oncology (Huntingt) 17:11–16

16.

Moore MJ, Goldstein D, Hamm J et al (2005) Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer. A phase III trial of the National Cancer Institute of Canada Clinical Trials Group [NCIC-CTG]. ASCO Annu Meet Proc 23:1s

17.

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 92:205–216PubMedCrossRef

18.

Ling J, Johnson KA, Miao Z et al (2006) Metabolism and excretion of erlotinib, a small molecule inhibitor of epidermal growth factor receptor tyrosine kinase, in healthy male volunteers. Drug Metab Dispos 34:420–426PubMed

19.

Pino MS, Shrader M, Baker CH et al (2006) Transforming growth factor alpha expression drives constitutive epidermal growth factor receptor pathway activation and sensitivity to gefitinib (Iressa) in human pancreatic cancer cell lines. Cancer Res 66:3802–3812PubMedCrossRef

20.

Zhang Y, Banerjee S, Wang Z et al (2006) Antitumor activity of epidermal growth factor receptor-related protein is mediated by inactivation of ErbB receptors and nuclear factor-kappaB in pancreatic cancer. Cancer Res 66:1025–1032PubMedCrossRef

21.

Graeven U, Kremer B, Sudhoff T et al (2006) Phase I study of the humanised anti-EGFR monoclonal antibody matuzumab (EMD 72000) combined with gemcitabine in advanced pancreatic cancer. Br J Cancer 94:1293–1299PubMedCrossRef

22.

Fossella FV, Lippman SM, Shin DM et al (1997) Maximum-tolerated dose defined for single-agent gemcitabine: a phase I dose-escalation study in chemotherapy-naive patients with advanced non-small-cell lung cancer. J Clin Oncol 15:310–316PubMed

23.

Okamoto I, Fujii K, Matsumoto M et al (2003) Diffuse alveolar damage after ZD1839 therapy in a patient with non-small cell lung cancer. Lung Cancer 40:339–342PubMed

24.

Shah NT, Kris MG, Pao W et al (2005) Practical management of patients with non-small-cell lung cancer treated with gefitinib. J Clin Oncol 23:165–174PubMedCrossRef

25.

Roychowdhury DF, Cassidy CA, Peterson P et al (2002) A report on serious pulmonary toxicity associated with gemcitabine-based therapy. Invest New Drugs 20:311–315PubMedCrossRef

26.

Hidalgo M, Siu LL, Nemunaitis J et al (2001) Phase I and pharmacologic study of OSI-774, an epidermal growth factor receptor tyrosine kinase inhibitor, in patients with advanced solid malignancies. J Clin Oncol 19:3267–3279PubMed

27.

Hirsch FR, Varella-Garcia M, McCoy J et al (2005) Increased epidermal growth factor receptor gene copy number detected by fluorescence in situ hybridization associates with increased sensitivity to gefitinib in patients with bronchioloalveolar carcinoma subtypes: a Southwest Oncology Group Study. J Clin Oncol 23:6838–6845PubMedCrossRef

28.

Bell DW, Lynch TJ, Haserlat SM et al (2005) Epidermal growth factor receptor mutations and gene amplification in non-small-cell lung cancer: molecular analysis of the IDEAL/INTACT gefitinib trials. J Clin Oncol 23:8081–8092PubMedCrossRef

Titel: Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors: phase IB trial
verfasst von: Tomislav Dragovich
Mark Huberman
Daniel D. Von Hoff
Eric K. Rowinsky
Paul Nadler
Debra Wood
Marta Hamilton
George Hage
Julie Wolf
Amita Patnaik
Publikationsdatum: 01.07.2007
Verlag: Springer-Verlag
Erschienen in: Cancer Chemotherapy and Pharmacology / Ausgabe 2/2007
Print ISSN: 0344-5704
Elektronische ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-006-0389-0

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Erlotinib plus gemcitabine in patients with unresectable pancreatic cancer and other solid tumors: phase IB trial