Chapter 095. Carcinoma of Unknown Primary (Part 6) pps

Carcinoma of Unknown Primary Part 6 Management of Disseminated CUP Patients who present with liver, brain, and adrenal metastatic disease usually have a poor prognosis.. In a phase II

Chapter 095 Carcinoma of

Unknown Primary

(Part 6)

Management of Disseminated CUP

Patients who present with liver, brain, and adrenal metastatic disease usually have a poor prognosis Beside primary peritoneal carcinoma, carcinomatosis presenting as CUP in other settings is not uncommon Gastric, appendicular, colon, pancreas, and cholangiocarcinoma are all possible primaries, and imaging, endoscopy, and pathologic data help in the evaluation

Traditionally, platinum-based combination chemotherapy regimens have been used to treat patients with CUP In a phase II study by Hainsworth and colleagues, 55 mostly chemotherapy-naive patients were treated with paclitaxel, carboplatin, and oral etoposide every 3 weeks The overall response rate was 47%,

with median overall survival duration of 13.4 months Briasoulis and colleagues reported similar response rates and survival durations in 77 patients with CUP who had been treated with paclitaxel and carboplatin In this study, patients with nodal

or pleural disease and women with peritoneal carcinomatosis had higher response rates and overall survival durations of 13 and 15 months, respectively Studies incorporating newer agents, including gemcitabine, irinotecan, and targeted agents, are showing higher response rates In a phase II randomized trial by Culine and colleagues, 80 patients were randomly assigned to receive gemcitabine with cisplatin or irinotecan with cisplatin; 78 patients were assessible for efficacy and toxicity Objective responses were observed in 21 patients (55%) in the gemcitabine and cisplatin arm and in 15 patients (38%) in the irinotecan and cisplatin arm The median survival was 8 months for gemcitabine and cisplatin and 6 months for irinotecan and cisplatin

The role of second-line chemotherapy in CUP is poorly defined Gemcitabine as a single agent has shown a partial response rate of 8%, and 25% of patients had minor responses or stable disease, with improved symptoms Combination chemotherapy as a second- and third-line treatment may result in a slightly improved response

Combination targeted therapy is being evaluated Hainsworth and colleagues studied the combination of bevacizumab and erlotinib in 51 patients; 25% were chemotherapy-naive and had advanced bone or liver metastases, while

the rest had been previously treated with 1 or 2 chemotherapy regimens Responses were noted in 4 patients (8%), and 30 patients (59%) experienced stable disease or a minor response The median overall survival was 8.9 months, with 42% of patients alive at 1 year

Historically, patients with CUP have been treated with "global" regimens that work for a variety of primary cancers With incremental improved responses over the past decade in known cancer types, we anticipate overall better response rates with newer regimens for selected CUP patients With a more robust immunohistochemical panel (directed approach) and new molecular data, one may

be able to create a more tailored algorithm for CUP patients

Summary

Patients with CUP should undergo a directed diagnostic search for the primary tumor on the basis of clinical and pathologic data Subsets of patients have prognostically favorable disease, as defined by clinical or histologic criteria, and may substantially benefit from aggressive treatment and expect prolonged survival However, for most patients who present with advanced CUP, the prognosis remains poor, with early resistance to available cytotoxic therapy Research into the metastatic phenotype will help us improve our understanding of CUP tumor biology Whether the CUP clone is a distinct molecular genotype-phenotype that is different from metastases of known primary tumors remains to

be elucidated The identification of specific CUP-related molecular and biochemical targets may help exploit therapeutic targeted agents for this entity

Further Readings

Abbruzzese JL et al: The biology of unknown primary tumors Semin Oncol 20:238, 1993 [PMID: 8503019]

Bugat R et al: 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, 2003

Culine S et al: Cisplatin in combination with either gemcitabine or irinotecan in carcinomas of unknown primary site: Results of a randomized phase

II study—trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01) J Clin Oncol 21:3479, 2003 [PMID: 12972523]

Dennis JL, Oien KA: Hunting the primary: novel strategies for defining the origin of tumours J Pathol 205:236, 2005 [PMID: 15641019]

Greco FA, Hainsworth JD: One-hour paclitaxel, carboplatin, and extended-schedule etoposide in the treatment of carcinoma of unknown primary site Semin

Oncol 24(6 Suppl 19):S19, 1997

Kende AI et al: Expression of cytokeratins 7 and 20 in carcinomas of the gastrointestinal tract Histopathology 42:137, 2003 [PMID: 12558745]

Lobins R, Floyd J: Small cell carcinoma of unknown primary Semin Oncol 34:39, 2007 [PMID: 17270664]

Olson JA Jr et al: Magnetic resonance imaging facilitates breast conservation for occult breast cancer Ann Surg Oncol 7:411, 2000 [PMID: 10894136]

Rusthoven KE et al: The role of fluorodeoxyglucose positron emission tomography in cervical lymph node metastases from an unknown primary tumor Cancer 101:2641, 2004 [PMID: 15517576]

Varadhachary GR et al: Diagnostic strategies for unknown primary cancer Cancer 100:1776, 2004 [PMID: 15112256]

Bibliography

Roh MS, Hong SH: Utility of thyroid transcription factor-1 and cytokeratin

20 in identifying the origin of metastatic carcinomas of cervical lymph nodes J Korean Med Sci 17:512, 2002 [PMID: 12172048]