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Chemotherapy (chemo) is recommended for most patients with cancer of unknown primary (CUP). Because chemo reaches all parts of the body, it is often useful in treating CUP, which usually is in many areas in most patients. If your doctor recommends chemo, it’s important that you understand the goals of your treatment.

Chemotherapy (chemo) is the use of drugs to treat cancer. Often, these drugs are injected into a vein intravenously (IV) or taken by mouth. They enter the bloodstream and reach much of the body, making this treatment potentially useful for cancers that have spread beyond where they started.

Chemo may be the main treatment for cancers that are advanced and are unlikely to be helped by local treatments such as surgery or radiation therapy. In some cases, it may be very effective in making tumors shrink or even go away completely. In other cases, chemo may be used to try to relieve symptoms caused by the cancer and may be able to help people live longer.

For cancers that appear to have been removed completely with surgery or radiation, chemo may be added to try to kill any remaining cancer cells in the body.

Before recent advances in molecular diagnosis, the tissue of origin remained unknown in most patients with CUP. Most patients received combination chemotherapy regimens, containing drugs active against a variety of cancers. These treatments were beneficial for some CUP patients.

Certain factors predicted which patients with CUP would benefit the most from chemo. They include:

• Tumor location in lymph nodes or soft tissues. By comparison, patients with involvement of the liver or bones may not be as likely to benefit from chemo.
• Few sites of metastatic disease
• Being female
• Laboratory results showing poorly differentiated carcinoma (the cancer cells do not look like normal cells)
• The ability to care for yourself and to perform regular daily activities and maintain good physical capabilities
• A blood test that shows normal levels of an enzyme called lactate dehydrogenase (LDH)
• A blood test that shows normal levels of a protein called albumin
• A blood test that shows a normal count for an immune cell called a lymphocyte

Chemotherapy for CUP adenocarcinomas and poorly differentiated carcinomas

For CUP that is an adenocarcinoma or a poorly differentiated carcinoma, many chemo combinations have been tested, and produce similar results. The drug combinations sometimes used include:

• Carboplatin plus paclitaxel (Taxol^?)
• Carboplatin plus docetaxel (Taxotere^?)
• Cisplatin plus gemcitabine (Gemzar^?)
• Cisplatin plus docetaxel
• Gemcitabine plus docetaxel
• Irinotecan (Camptosar^?) plus carboplatin
• Irinotecan plus gemcitabine
• Oxaliplatin (Eloxatin^?) plus 5-fluorouracil and leucovorin (folinic acid)
• Oxaliplatin plus capecitabine (Xeloda^?)

Chemotherapy for CUP squamous cell cancers (carcinomas)

If chemotherapy is to be used for a CUP that is a squamous cell cancer, options include:

• Cisplatin or carboplatin plus a taxane (paclitaxel or docetaxel)
• Cisplatin plus 5-fluorouracil
• Cisplatin plus gemcitabine
• Oxaliplatin (Eloxatin^?) plus 5-fluorouracil and leucovorin (folinic acid)

Chemotherapy for CUP neuroendocrine cancers (carcinomas) 

Patients with poorly differentiated neuroendocrine carcinomas are often treated with the same chemo used for small cell cancer of the lung: a platinum drug (cisplatin or carboplatin) and etoposide.

Patients who have CUP and are found to have well-differentiated neuroendocrine cancer on a biopsy are treated with drugs such as:

• Octreotide (Mycapssa) or lanreotide (Somatuline)
• Lutetium Lu-177 dotatate (Lutathera)
• Capecitabine
• Temozolomide ?

More information about the treatment of well-differentiated neuroendocrine cancers can be found in Gastrointestinal Carcinoid Tumors, Lung Carcinoid Tumor, and Pancreatic Cancer.

Possible side effects of chemotherapy

Chemo drugs can cause side effects, depending on the specific drugs used, their doses, and how long treatment lasts.

Common side effects of chemo include:

• Hair loss
• Mouth sores
• Loss of appetite
• Diarrhea or constipation
• Nausea and vomiting
• Increased chance of infections
• Problems with bruising or bleeding
• Fatigue or shortness of breath

Along with the risks above, some chemo drugs can cause other side effects.

Ask your health care team what side effects you can expect from the specific drugs you will get. Be sure to tell your doctor or nurse if you do have side effects, as there are often ways to manage them. For example, drugs can be given to help prevent or reduce nausea and vomiting.