Cancer of Unknown Primary Treatment Protocols 

Updated: Dec 01, 2015
  • Author: Winston W Tan, MD, FACP; Chief Editor: Jules E Harris, MD, FACP, FRCPC  more...
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Treatment Protocols

Treatment protocols for cancer of unknown primary are provided below, including treatment for metastasis to cervical lymph nodes, in women with isolated axillary adenopathy, for metastatic melanoma to a single nodal site, and for cancer of unknown primary in unselected patients, as well as common chemotherapeutic agents in clinical practice. [1]

General treatment recommendations

See the list below:

  • Chemotherapy for patients with cancer of unknown primary is aimed at prolonging survival and relieving any related symptoms

  • Chemotherapy should be considered for patients who are symptomatic or for asymptomatic patients with an aggressive cancer and should be based on the histologic type of the cancer [2]

  • Patients in whom combination therapy fails may benefit from single-agent treatment with gemcitabine, with median time to progression of 5mo

  • Patients with cancer of unknown primary should always be offered a clinical trial as an option for treatment

Cancer of unknown primary origin treatment recommendations

Adenocarcinoma [2, 3, 4, 5] :

Adenocarcinomas respond to cisplatin-based combination chemotherapy. However, various studies have shown that treatment with carboplatin, gemcitabine, irinotecan, and docetaxel have also been effective. [2]

  • Paclitaxel 200 mg/m2 IV infusion over 1h on day 1 plus carboplatin AUC 6 on day 1 (see the Carboplatin AUC Dose Calculation [Calvert formula] calculator) plus etoposide 50 mg PO alternating with 100 mg daily on days 1-10; every 21d for 2-3 cycles; then restage (patients are often treated with 6 cycles up to best response or up to dose-limiting toxicities) or

  • Paclitaxel 200 mg/m2 IV infusion over 3h on day 1 plus  carboplatin AUC 6 on day 1; every 21d or

  • Docetaxel 65 mg/m2 IV on day 1 plus  carboplatin AUC 6 on day 1; every 21d or

  • Gemcitabine 1250 mg/m2 IV on days 1 and 8 plus cisplatin 100 mg/m2 IV on day 1; every 21d or

  • Gemcitabine 1000 mg/m2 IV on days 1 and 8 plus  docetaxel 75 mg/m2 IV on day 8; every 21d or

  • Gemcitabine 1000 mg/m2 IV on days 1 and 8 plus irinotecan 100 mg IV on days 1 and 8; every 21d cycle for 6 cycles; restage every 2-3 cycles with computed tomography (CT) and bone scans

  • Trials using combination therapy with bevacizumab, erlotinib, paclitaxel, and carboplatin have been evaluated, showing activity as first-line therapy in previously untreated patients; response rate, progression-free survival time, and overall survival time achieved with this regimen are among the best reported to date in the first-line treatment of CUP patients however, more data is needed [6]

  • Trials using a combination of oxaliplatin and leucovorin with bolus and continuous infusion of 5-fluorouracil every two weeks requires further study. [7]

Squamous cell carcinoma [2, 3, 4, 5] :

Treatments that include platinum-based chemotherapy are used in patients with squamous cell carcinoma. The most commonly used chemotherapeutic agents are 5-FU and cisplatin. Alternatively, docetaxel has also been used in combination with cisplatin.

  • Paclitaxel 175 mg/m2 IV infusion over 3h on day 1 plus  cisplatin 100 mg/m2 IV on day 2 plus 5-FU (5-fluorouracil) 500 mg/m2/day IV continuous infusion over 120h every 21d or

  • Docetaxel 75 mg/m2 IV on day 1 plus  cisplatin 75 mg/m2 IV on day 1 plus  5-FU 750 mg/m2/day IV continuous infusion on days 1-5; every 21d

Neuroendocrine tumors [2, 3, 4, 5] :

Poorly differentiated neuroendocrine tumors are generally responsive to combination chemotherapy. Commonly used chemotherapeutic agents include paclitaxel, etoposide, and platinum agents.

  • Etoposide was given at a dose of 100 mg/m2 every day for 3d plus  cisplatin 45 mg/m2 on days 2-3 as a continuous IV infusion; repeated every 4wk [8]

Metastasis to cervical lymph nodes:

  • Radical radiation therapy with curative intent is administered to the neck and possible site of origin

  • Preoperative radiation therapy is followed by radical neck dissection

  • Radical neck dissection is followed by radiation to possible sites of origin [9]

Isolated axillary adenopathy in women:

  • Currently, management is based on the guidelines for stage II breast cancer [10]

  • Modified radical mastectomy with axillary node dissection has been advocated

  • When these patients are treated with local excision or as having primary breast cancer, 50% of patients achieve 2-10y survival

Metastatic melanoma to a single nodal site:

  • Five percent of patients with malignant melanoma may present with nodal metastasis in the absence of a documented primary site; these patients should be treated with radical lymph node dissection

Inguinal node metastasis:

  • Treatment can involve groin dissection alone or with radiation and chemotherapy

  • Some patients may benefit from local excision with or without radiation therapy

Various molecular panels are available for the clinician to use to help determine the primary cancer. If the clinician believes this will help him or her tailor the treatment best for the patient, then the panels should be ordered. The test might show that a tumor is sensitive to a drug that does not make sense based on clinical findings; in such a setting, it is important to use the best clinical judgement to treat the patient. How best to use this test is still evolving at this time.