Cancer Treatment Today » Unknown Primary Site

Second-line Chemotherapy for Occult Primary – pro

M Levin, MD — Mon, 02 Jul 2012 14:55:07 +0000

Management of cancers of unknown origin is complex. When the primary site is not identified and when it does not fall neatly into certain specific clinical patterns, empiric broad-spectrum chemotherapy is recommended by NCCN and is generally acceptable. The issue remains second line chemotherapy for adenocarcinooma of occult primary. Combination sequential chemotherapy with paclitaxel, carboplatin, and oral etoposide followed by gemcitabine and irinotecan proved to be an active and useful therapy for some patients with unknown primary carcinomas. I reviewed the literature and found several phase II trials of second line chemotherapy but not with this regimen. For example, on ongoing trial is a phase II trial, to evaluate the feasibility and efficacy of the oxaliplatin/capecitabine combination in patients who have had one previous chemotherapy regimen for the treatment of carcinoma of unknown primary site. Gemcitabine, an active drug in several solid tumors, has also found to be useful as secondary therapy for some patients with carcinoma of unknown primary site. Phase II trials of gemcitabine and topotecan in second-line therapy of unknown primary cancer are underway. Still, no phase III trials and no guidelines recommandations could be located.

Greco, F. Anthony , Rodriguez, Gladys I. , Shaffer, Don W. , Hermann, Robert , Litchy, Sharlene , Yardley, Denise A. , Burris, Howard A., III , Morrissey, Lisa H. , Erland, Joan B. , Hainsworth, John D. Carcinoma of Unknown Primary Site: Sequential Treatment with Paclitaxel/Carboplatin/Etoposide and Gemcitabine/Irinotecan: A Minnie Pearl Cancer Research Network Phase II Trial Oncologist 2004 9: 644-652;

F. Anthony Greco et al, Carcinoma of Unknown Primary Site: Sequential Treatment with Paclitaxel/Carboplatin/Etoposide and Gemcitabine/Irinotecan: A Minnie Pearl Cancer Research Network Phase II Trial The Oncologist, Vol. 9, No. 6, 644-652, November 2004;

nccn.org, occult primary

K. Fizazi et al, Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Ann Oncol (2011) 22 (suppl 6): vi64-vi68.

Chemotherapy of Cancer of Unknown Primary Site – pro

M Levin, MD — Mon, 02 Jul 2012 14:52:09 +0000

Lay Summary: Metastatic cancers of unknown primary source can be treated with broad-spectrum chemotherapy.

Management of cancers of unknown origin is complex. When the primary site is not identified and when it does not fall neatly into certain specific clinical patterns, empiric broad-spectrum chemotherapy is recommended by NCCN and is generally acceptable. During the 1990s, several new antineoplastic agents with novel mechanisms of action have been introduced into clinical practice. Some of these agents, including the taxanes (paclitaxel, docetaxel), gemcitabine, vinorelbine, and the topoisomerase I inhibitors (irinotecan, topotecan) are active against a wide variety of solid tumors. Therefore, these drugs offer promise in the empiric treatment of carcinoma of unknown primary site. Newer agents, like sorafenib, bevacizumab, antineoplaston, CS-1008 (humanized anti-CD-5 antibody), BMS-690514, ZD1839, are currently being tested in various clinical trials. Combinations of older drugs like carboplatin with weekly paclitaxel, and gemcitabine combinations are recommended by NCCN in first line only.

K. Fizaz et al, Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up, Ann Oncol (2011) 22 (suppl 6): vi64-vi68.

http://nccn.org/professionals/physician_gls/PDF/occult.pdf

Greco FA, Hainsworth JD. Cancer of unknown primary site. In: De Vita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice. 2005:2213-34.

Montero AJ, Varadhachary GR, Abbruzzese JL. Unknown Primary Carcinomas. In: Kantarjian HN, Koller CM, Wolff RA. MD Anderson Manual of Medical Oncology. McGraw Hill; 2006:937-954.

PET for Unknown Primary Site, Occult Primary – pro

M Levin, MD — Mon, 02 Jul 2012 14:50:02 +0000

Lay Summary: PET and PET/CT are useful to the find primary site of metastases when it is not known.

FDG-PET is useful to detect the primary tumor in patients with unknown primary tumors, according to a recent meta-analysis, which suggests that PET’s intermediate specificity, high sensitivity, and concomitant low false-negative rate offer substantial benefits in the initial stages of oncologic patient management.

Survival is low for patients with unknown primary tumors: less than six months from the time of initial diagnosis, and 11% and 6% at three-year and five-year follow-up, respectively.

At initial diagnosis, unknown primary tumors occur between 0.5% and 7% of oncologic cases. At follow-up, the prevalence is between 3% and 15%. Also, unknown primary tumors have no specific metastatic location. The meta-analysis of the literature found F-18 FDG-PET detected the primary tumor in 43% of 298 patients with unknown primary tumors. Sensitivity and specificity were 87% and 71%, respectively. Researchers also analyzed 15 studies that met the inclusion criteria.

Survival is low for patients with unknown primary tumors: less than six months from the time of initial diagnosis, and 11% and 6% at three-year and five-year follow-up, respectively.

Value of restaging PET had not been established defintievley for patients on treatment of occult primary cancer.

Regelink G, Brouwer J, De Bree R, et al. Detection of unknown primary tumors and distant metastases in patients with cervical metastases: value of FDG-PET versus conventional modalities. Eur J Nucl Med 2002;29:1024-1030.

Reske SN, Kotzerke J. FDG-PET for clinical use. Results of the 3 rd German Interdisciplinary Consensus Conference. Eur J Nucl Med 2001;28:1707-1723.

nccn.org. occult primary, 2018 OCC-3

Ahmed MohamedWafaie et al, Cancer of unknown primary origin: Can FDG PET/CT have a role in detecting the site of primary?The Egyptian Journal of Radiology and Nuclear Medicine. Volume 49, Issue 1, March 2018, Pages 190-195

nccn.org. occult primary OCC-3

Lebech AM et al, Whole-Body 18F-FDG PET/CT Is Superior to CT as First-Line Diagnostic Imaging in Patients Referred with Serious Nonspecific Symptoms or Signs of Cancer: A Randomized Prospective Study of 200 Patients.J Nucl Med. 2017 Jul;58(7):1058-1064

Gemcitabine and Carboplatin for Unknown Primary – pro

M Levin, MD — Mon, 02 Jul 2012 14:47:40 +0000

Among the agents that NCCN recommends is gemcitabine and cisplatin. The doses that it recommends are 1250mg/m2 D1 and 8 and 100mg/m2 every 3 weeks. Gemcitabine, an active drug in several solid tumors, has also found to be useful as secondary therapy for some patients with carcinoma of unknown primary site. Carboplatin is recommended by NCCN in combination with other drugs as well for unknown primary but with gemcitabine it recommends cisplatin. The selection of cisplatin and not carboplatin is eclectic, in my opinion, as phase II trials support carboplatin also.

PDQ says: “The majority of patients will not have a definable primary source. For such patients, a variety of combination chemotherapy approaches have been tried with little success. No treatment can be considered standard at present. Therefore, such patients should be considered for available clinical trials.” The NCCN clearly does not agree that there is no standard therapy and carboplatin should be considered standard with gemcitabine as well as cisplatin. The combination of gemcitabine and carboplatin has the advantage of being able to be administered rapidly in an outpatient setting with myelosuppression (usually dose dependent) being the only frequent major toxicity. Significant nausea, vomiting and alopecia are rare. The spectrum of activity of the combination is such that it would appear to be an ideal combination to use in this setting, provided that colorectal cancer, where carboplatin is inactive, can be reasonably excluded. In most of these settings carboplatin has been shown to be equivalent to cisplatin.
nccn.org, occult primary

nccn.org, occult primary

K B Pittman et al, Gemcitabine and carboplatin in carcinoma of unknown primary site: a phase 2 Adelaide Cancer Trials and Education Collaborative study British Journal of Cancer (2006) 95, 1309–1313.

Gemcitabine plus carboplatin is “an active and very well-tolerated” therapy against carcinoma of unknown primary site
Inpharma, Volume 1, Number 1570, 2007-01-13 , pp. 18-18(1)

K. Fizaz et al, iCancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol (2011) 22 (suppl 6): vi64-vi68.

NCCN, Occult Primary, OCC-B, 1-4, 2015

Erbitux for Squamous Cell Cancer of Unknown Primary Site – pro

M Levin, MD — Mon, 02 Jul 2012 14:43:49 +0000

When the primary site is not identified and when it does not fall neatly into certain specific clinical patterns, empiric broad-spectrum chemotherapy is recommended by NCCN and is generally acceptable. The issue remains second line chemotherapy. Erbitux is approved for squamous cell cacner of head and neck and is an attractive candidate for unknown primary. Unfortunately, these patients have a dismal prognosis despite management with a variety of chemotherapeutic combinations in small clinical studies. A recent meta-analysis showed no evidence of superior efficacy of any of the administered regimens incorporating platinum salts, taxanes or new generation cytotoxic compounds (gemcitabine, vinca alkaloids, irinotecan). Modest if any survival prolongation and symptom palliation with preservation of quality of life are the only realistic aims of therapy for these patients. Consequently, low-toxicity patient-convenient chemotherapy regimens should be administered to reasonably fit poor-risk patients. Currently neither ESMO nor NCCN recommend Erbitux even in first line. NCCN recommendations do nto include Erbitux(OCC-B, 1) and enitehr recommends second line chemotherapy.

N. Pavlidis1, E. Briasoulis, G. Pentheroudakis and On behalf of the ESMOCancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
Ann Oncol (2010) 21 (suppl 5): v228-v231.

K. Hemminki et al, Power and limits of modern cancer diagnostics: cancer of unknown primary
Ann Oncol (2012) 23(3): 760-764

nccn.org, occult primary,2012

Read the Layperson version here.