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. Among the agents that NCCN recommends is gemcitabine and cisplatin. The NCCN also recommends Paclitaxel or docetaxel with carboplatin. There are many trials with carboplatin instead of cisplatin and at various doses. The use of carboplatin should not be considered investigational.
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