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International Journal of Clinical Oncology

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01-04-2013 | Original Article

A phase II study to evaluate the efficacy and toxicity of oxaliplatin in combination with gemcitabine in carcinoma of unknown primary

Authors: Heather Carlson, Renato Lenzi, Martin N. Raber, Gauri R. Varadhachary

Published in: International Journal of Clinical Oncology | Issue 2/2013

Abstract

Background

Preclinical and clinical data suggest synergy for gemcitabine and oxaliplatin. These agents were tested in several known cancers that also comprise the common carcinoma of unknown primary (CUP) subtypes; namely, lung and pancreaticobiliary profiles.

Methods

The study enrolled 29 patients of whom 28 patients were eligible for treatment. Gemcitabine was given at 1,000 mg/m² as a fixed dose rate infusion and oxaliplatin was infused at 100 mg/m² every 2 weeks with restaging performed after 3 cycles at 6 weeks.

Results

The study reported one complete response (CR) (4%), 6 patients with a partial response (PR) (25%), and 13 with stable disease (SD) (54%); and 4 patients had progressive disease (PD) (17%) on restaging. Median overall survival (OS) and progression-free survival were 12.8 months (95% confidence interval [CI] 8.5–18.5) and 3.1 months (95% CI 1.7–6), respectively. The 1-year OS was 54%. The most common grade 3 toxicities were nausea (22%), vomiting (15%), and fatigue (11%). There were no grade 4 toxicities. This study was closed early as we moved from an empiric therapy platform to a more individualized approach.

Conclusions

Gemcitabine and oxaliplatin is a well-tolerated regimen in CUP with similar outcomes to previously documented CUP studies. In selected good performance status patients this combination may serve as a first-line doublet chemotherapy option for CUP patients (clinicaltrials.gov ID:NCT00353145).

Abbruzzese JL, Abbruzzese MC, Hess KR et al (1994) Unknown primary carcinoma: natural history and prognostic factors in 657 consecutive patients. J Clin Oncol 12(6):1272–1280PubMed

Glover K, Varadhachary GR, Lenzi R et al (2008) Unknown primary cancer. In: Abelhoff M (ed) Clinical oncology, 4th edn. Elsevier, Philadelphia, pp 2057–2074

Bugat R, Bataillard A, Lesimple T et al (2002) Summary of the standards, options and recommendations for the management of patients with carcinoma of unknown primary site. Br J Cancer 89(Suppl 1):S59–S66

Hainsworth JD, Erland JB, Kalman LA et al (1997) Carcinoma of unknown primary site: treatment with 1-hour paclitaxel, carboplatin, and extended-schedule etoposide. J Clin Oncol 15(6):2385–2393PubMed

Briasoulis E, Kalofonos H, Bafaloukos D et al (2000) Carboplatin plus paclitaxel in unknown primary carcinoma: a phase II Hellenic Cooperative Oncology Group Study. J Clin Oncol 18(17):3101–3107PubMed

Briasoulis E, Fountzilas G, Bamias A et al (2008) Multicenter phase-II trial of irinotecan plus oxaliplatin [IROX regimen] in patients with poor-prognosis cancer of unknown primary: a Hellenic Cooperative Oncology Group study. Cancer Chemother Pharmacol 62(2):277–284PubMedCrossRef

Schneider BJ, El-Rayes B, Muler JH et al (2007) Phase II trial of carboplatin, gemcitabine, and capecitabine in patients with carcinoma of unknown primary site. Cancer 110(4):770–775PubMedCrossRef

Palmeri S, Lorusso V, Palmeri L et al (2006) Cisplatin and gemcitabine with either vinorelbine or paclitaxel in the treatment of carcinomas of unknown primary site: results of an Italian multicenter, randomized, phase II study. Cancer 107(12):2898–2905PubMedCrossRef

Hainsworth JD (2006) Bevacizumab plus erlotinib in patients (pts) with carcinoma of unknown primary site: a phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 24(18S):3033

10.

Hainsworth JD, Spigel DR, Raefsky EL et al (2005) Combination chemotherapy with gemcitabine and irinotecan in patients with previously treated carcinoma of an unknown primary site: a Minnie Pearl Cancer Research Network Phase II trial. Cancer 104(9):1992–1997PubMedCrossRef

11.

Faivre S, Raymond E, Woynarowski JM et al (1999) Supraadditive effect of 2′,2′-difluorodeoxycytidine (gemcitabine) in combination with oxaliplatin in human cancer cell lines. Cancer Chemother Pharmacol 44(2):117–123PubMedCrossRef

12.

Faivre S, Chan D, Salinas R et al (2003) DNA strand breaks and apoptosis induced by oxaliplatin in cancer cells. Biochem Pharmacol 66(2):225–237PubMedCrossRef

13.

Louvet C, Labianca R, Hammel P et al (2005) Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial. J Clin Oncol 23(15):3509–3516PubMedCrossRef

14.

Weissman C, Reynold C, Neubauer M et al (2011) A phase III randomized trial of gemcitabine-oxaliplatin versus carboplatin-paclitaxel as first-line therapy in patients with advanced non-small cell lung cancer. J Thorac Oncol 6(2):358–364PubMed

15.

Franciosi V, Barbieri R, Aitini E et al (2003) Gemcitabine and oxaliplatin: a safe and active regimen in poor-prognosis advanced non-small cell lung cancer patients. Lung Cancer 41(1):101–106PubMedCrossRef

16.

Halim A, Ebrahim M, Saleh Y (2011) A phase II study of outpatient biweekly gemcitabine-oxaliplatin in advanced biliary tract carcinomas. Jpn J Clin Oncol 41(2):217–224PubMedCrossRef

17.

Andre T, Reyes-Vidal JM, Fartoux L et al (2008) Gemcitabine and oxaliplatin in advanced biliary tract carcinoma: a phase II study. Br J Cancer 99(6):862–867PubMedCrossRef

18.

Varadhachary G, Talantov D, Raber M et al (2008) Molecular profiling of carcinoma of unknown primary and correlation with clinical evaluation. J Clin Oncol 26(7):4442–4448PubMedCrossRef

19.

Louvet C, André T, Lledo G et al (2002) Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study. J Clin Oncol 20(6):1512–1518PubMedCrossRef

20.

Alberts SR, Townley PM, Goldberg RM et al (2003) Gemcitabine and oxaliplatin for metastatic pancreatic adenocarcinoma: a North Central Cancer Treatment Group phase II study. Ann Oncol 14(4):580–585PubMedCrossRef

21.

Therasse P, Arbuck S, Eisenhauer E et al (2000) New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 92(3):205–216PubMedCrossRef

22.

Varadhachary GR, Raber MN, Matamoros A et al (2008) Carcinoma of unknown primary with a colon-cancer profile–changing paradigm and emerging definitions. Lancet Oncol 9(6):596–599PubMedCrossRef

23.

Tot T (1999) Adenocarcinomas metastatic to the liver: the value of cytokeratins 20 and 7 in the search for unknown primary tumors. Cancer 85(1):171–177PubMedCrossRef

24.

Rubin BP, Skarin AT, Pisick E et al (2001) Use of cytokeratins 7 and 20 in determining the origin of metastatic carcinoma of unknown primary, with special emphasis on lung cancer. Eur J Cancer Prev 10(1):77–82PubMedCrossRef

25.

Varadhachary GR, Spector Y, Abbruzzese JL et al (2011) Prospective gene signature study using microRNA to identify the tissue of origin in patients with carcinoma of unknown primary. Clin Cancer Res 17(12):4063–4070PubMedCrossRef

Title: A phase II study to evaluate the efficacy and toxicity of oxaliplatin in combination with gemcitabine in carcinoma of unknown primary
Authors: Heather Carlson
Renato Lenzi
Martin N. Raber
Gauri R. Varadhachary
Publication date: 01-04-2013
Publisher: Springer Japan
Published in: International Journal of Clinical Oncology / Issue 2/2013
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI: https://doi.org/10.1007/s10147-011-0366-4

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Abstract

Background

Methods

Results

Conclusions

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