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Types of treatment

Chemotherapy (Chemo)

(Cytotoxic) chemotherapy drugs – in essence, poisons – are usually injected into the bloodstream, but sometimes taken by mouth, to try and cure or reduce the cancer tumours. It is the most common way of dealing with metastatic cancers like CUP  that have spread.

In the event that your treatment includes surgery, you may hear the terms Adjuvant chemotherapy (used after surgery to mop-up cells; or Neoadjuvant chemotherapy (used before surgery to reduce the size of a tumour).

Where they can, oncologists are increasingly using ‘targeted’ therapies aimed at specific cell proteins or signalling pathways targets inside cancer cells; but because of the unspecific nature of CUP it may be necessary to use drugs that have multiple targets trying to interfere with more than one protein or signalling pathway in the cancer process. Systemic chemo affects the whole body and works by targeting rapidly dividing cells to kill them or stop them spreading. The drugs are unable to tell the difference between cancerous and healthy cells which is why, for example, some chemo treatments make the hair fall out or cause diarrhoea, (normal cells in the scalp and intestine have a high turnover).

All chemotherapies have side effects and the side effects will affect different people in different ways. The cancer doctor (oncologist) will be balancing the chemo’s toxicity with the potential benefit, and the ‘performance status’ of the patient (including their tolerance of the drugs). The effect of the chemicals in the chemo depends on the dose but, as this website on making sense of chemicals argues, we shouldn’t be too hung-up about ingesting chemicals. Where there are side effects of chemo treatments, such as nausea, the doctor will seek to reduce them with additional drugs.

The decision to have chemotherapy needs careful consideration. It is a very personal decision that belongs to the patient; but the decision should be made with advice and support from healthcare professionals. They will advise on the benefits that can realistically be expected. (See also Treatment Decisions on this page).

Different cancer cells, and the processes involved in the spread of cancer, respond to different drugs. CUP patients are likely to have varied (heterogeneous) cancer cells. Because of their genetic variability, the tumour cells are not uniformly sensitive to cytotoxic drugs. A combination of drugs is therefore usual to get the best effect (and Oncologists are constantly trying out new combinations to improve treatment). Chemo treatment is used increasingly (there was a 60% increase between 2004-2008 in England and Wales) because there are undoubted benefits for many patients in terms of quality of life, remission, prolongation of life or cure.

Patients receiving chemo should be given written information about their drugs and potential side effects. Information should also be provided about where to go in an emergency and who to contact by phone if problems arise (24 hours).

In short, there are many different chemotherapy options but to be most effective the treatment needs to be tailored to the (likely) site of origin – the primary site. There is an element of “hit or miss” with Chemotherapy. Every different mutation requires different treatment. Even if the primary site has been correctly deduced every patient is different and, rather like finding the right medicine for a chest infection, one chemo combination may be more effective than another; and one treatment may become less effective over time if a cancer is, or becomes, ‘chemo-resistant’. Unfortunately, cancer cells are very clever and do what they can to hide (as in CUP) and then evolve as they are hit with chemotherapy (think of an underground system where one station is closed but you can still get to your destination on a different, albeit less direct, route).

Therapeutic Ratio. You may wonder about the time gap between chemo sessions. The gap is calculated to allow time for the body to repair the normal cells but not the cancer cells.

Examples of chemotherapy drugs used by the NHS with CUP patients

The oncologist will take into account the pathological characteristics of the tumour, the toxicity profile of the drugs, their ease of administration and response rate, and the patient’s fitness when choosing which treatment to use. He or she will inform the patient about the potential benefits and risks of treatment weighed against not receiving chemo but receiving only ‘best supportive care’. Where there are no clinical features suggesting a specific treatable syndrome, possible (combination) regimes include:
• ECF (Epirubicin, Cisplatin and Fluorouracil 5FU)
• ECX (Epirubicin, Cisplatin and Capecitabine)
• Cisplatin and Gemcitabine
• Carboplatin and Gemcitabine
• Carboplatin and Taxol
• Capecitabine
• Oxaliplatin and modified de Gramont (OxMdG)/Capecitabine.

If there are indications that the CUP patient has a specific presentation such as peritoneal adenocarcinoma, axillary adenocarcinoma (in females), squamous cell carcinoma isolated to head and neck nodes, poorly differentiated midline CUP, neuroendocrine CUP, the oncologist may follow a path related specifically to protocols for site-specific tumours such as breast, head and neck, urology etc.

It should be noted that other drugs may be added to achieve the best results and reduce side effects. If a person is on a clinical trial then it is possible a new drug, or a new combination, may be tested. Macmillan Cancer Support have an excellent site giving details of treatments and the drugs shown above. There is a good guide here from Cancer Care to understand side effects e.g. nausea, mouth sores, nerve damage, infections etc., and what you can do about them.

Radiation therapy (Radiotherapy)

Radiotherapy uses radiation to destroy cancer cells in the treatment area. It’s usually given by focussing X-ray beams very precisely at a tumour, but it can be given internally by drinking liquid, having an injection or by having a radioactive implant in the body. In some instances it can be used to treat the whole body. The radiation kills the cancer cells by cumulative damage.

As with chemo, it is usually given over a number of sessions but, unlike chemo, the sessions tend to be every day for a number of days. It is possible that some damage may occur to neighbouring healthy cells but this damage usually repairs quickly (allowing the small gap between sessions).

The precise treatment will depend on the type, location and stage of the tumour as well as the health of the patient and the purpose of the treatment. The doctors will determine the tolerance of the patient’s normal tissue and the cancer to determine the level of radiation. The main purposes may be curative (to seek a long lasting cure or reduce the chances of the treated cancer cells returning) or palliative (reducing or slowing the symptoms).

Hormone therapy

Hormone (or Endocrine) therapy involves using sex hormones to treat  ‘hormone sensitive’ or ‘hormone dependent’ cancers such as those of breast, prostate, and womb cancers where the cancer cells are stimulated to grow by oestrogen (breast cancer) or testosterone (prostate cancer). Hormone treatments are also sometimes used for kidney cancer and for melanoma. Hormone therapy can also be used in combination with another procedure, for example to shrink a tumour before radiotherapy or surgery.


Immunotherapy attempts to stimulate the immune system to reject cancer and destroy tumours.This can be either through immunization of the patient, in which case the patient’s own immune system is trained to recognize tumour cells as targets to be destroyed, or through the administration of drugs designed to recruit the patient’s immune system to destroy tumour cells.


Surgery, where it is possible, offers probably the best option for offering a cure with most cancers but is often not appropriate for CUP patients. Unless the primary site of the cancer is identified the root cause of the metastatic cancer is not being addressed. Secondary cancers may be treated by surgery for palliative reasons.

(A papyrus from ancient Egypt in 1500 B.C. indicates that cancer was treated by cauterization to destroy tissue with a hot instrument and surface tumours were surgically removed, much as today.)

Tackling cancer pain

Particularly for those who have surgery and for advanced cancer patients it is important to control pain where it occurs. Palliative and supportive care  in general is explained in this section.  A ‘toolkit for patients and families’ on Tackling Cancer Pain is being developed by Dr Nic Hughes, Senior Research Fellow in Palliative Care at the University of Leeds. Please note that this resource is presently under development and the author is seeking comments (contact us if you want any passed on). We think it an excellent resource and will replace the draft with the final version when it is available, but in the meantime it gives patients and carers a way of understanding and communicating any pain.