The treatment of solid tumours involves the combined use of surgery, radiotherapy and chemotherapy. In the earlier stages surgery alone may be curative in many solid tumours, but may fail because of inadequate local excision with residual microscopic disease or because of disseminated micro metastases present at the time of diagnosis. Radiotherapy, similarly, is a local treatment which can often be used after surgery to reduce the chance of local recurrence. Good examples of this are breast cancer, where the use of surgery plus radiotherapy makes it possible to carry out breast-conserving surgery, and in rectal cancer, where local relapse in the pelvis can be reduced by the addition of radiotherapy. In some solid tumours, like early laryngeal cancer, radiotherapy can be used on its own with curative intent. It also has an important role in palliative treatment.
Chemotherapy is systemic treatment which can reach any part of the body with an adequate blood supply and is therefore normally used to treat disseminated cancer. Only a minority of metastatic solid cancers can routinely be cured with chemotherapy. These include testicular cancer, choriocarcinoma and childhood solid tumours. In other advanced solid tumours, chemotherapy may cure a small minority but it is usually given with the intention of prolonging life and relieving symptoms. In this situation it may be used to reduce the volume of the tumour without any realistic hope of eradicating disease. When chemotherapy is used without prospect of cure it is essential that care is taken choosing drugs with the least sideeffects. The development of new less toxic chemotherapeutic drugs and more effective antiemetics have done much to reduce the side-effects of chemotherapy. Chemotherapy is increasingly being used in patients who have had surgical clearance of their primary tumour but are at high risk of relapse from metastatic disease at distant sites. When used in this situation as adjuvant chemotherapy, there is a much greater chance of eradicating the tumour than when chemotherapy is given at the time of clinical relapse.
Breast cancer is the commonest cancer in women. Although surgical removal of the primary tumour is usually possible, most women will eventually relapse with metastatic disease.
Adjuvant therapy immediately following surgery has reduced the number of women dying from breast cancer by about 25%. A meta-analysis of all randomized trials of adjuvant therapy in breast cancer has shown conclusively that adjuvant chemotherapy, most commonly cyclophosphamide, methotrexate and 5-fluorouracil, for 6 months reduces the death rate by about 25% in premenopausal node-positive women. Adjuvant tamoxifen given for 2-5 years reduces death from breast cancer by a similar amount in postmenopausal patients. Trials to improve these results further are in progress.
Patients with established metastatic disease are treated with hormonal therapy or chemotherapy. Women who have high levels of oestrogen receptors in their tumour have a greater chance of responding to hormonal treatments. In addition certain clinical features can predict the likelihood of responding to hormonal manipulations.
1 More likely to respond to hormonal treatment
(a) Receptor positive
(b) Long interval from initial surgery to time of relapse
(c) Metastatic disease in bone and soft tissue
2 Less likely to respond to hormonal treatments
(a) Receptor negative
(b) Short interval from initial surgery to relapse
(c) Liver metastases or lymphangitis carcinomatosa
Endocrine therapy is usually tried first in those patients who have characteristics suggesting they are likely to respond. Useful remissions can be obtained for years and many elderly patients may live a normal life expectancy despite still having residual breast cancer. A range of hormonal manipulations are available:
(a) Cessation of ovarian function
(ii) Radiation-induced ovarian ablation
(iii) LHRH analogue with down-regulation of the pituitary
(c) Aromatase inhibitors, e.g. aminoglutethamide
In patients who are unlikely to respond to hormonal treatment or who fail therapy with hormones, chemotherapy is used. If chosen carefully chemotherapy can provide good quality palliation and prolongation of life. The most common regimens used include:
• CMF (cyclophosphamide, methotrexate, 5-fluorouracil)
• MMM (mitozantrone, methotrexate and mitomycin C
• Doxorubicin and cyclophosphamide
The first two regimens are often very well tolerated and cause little in the way of nausea and vomiting and do not usually cause hair loss. Single agent mitozantrone is often used in elderly unfit patients and is usually well tolerated.
This is the commonest cancer in males, and second commonest cancer in females after breast cancer. It is also the most preventable cancer as over 90% is directly related to cigarette smoking. For practical purposes lung cancer can be divided into small-cell lung cancer, comprising about 20%, and non-small-cell lung cancer, comprising 80%. In non-small-cell lung cancer surgery should be considered in all cases although only one-quarter of patients will be operable and only one-quarter of them will be cured. Radiotherapy may provide useful palliation in inoperable patients and very good symptom relief in metastatic disease. Chemotherapy is still experimental in non-small-cell lung cancer and its role is not yet established. In small-cell lung cancer the disease has almost always disseminated by the time of diagnosis and surgery is thus inappropriate. As opposed to non-small-celliung cancer, this tumour is very chemosensitive and radiosensitive and the majority of patients will respond to combination chemotherapy (e.g. mitomycin, ifosfamide and cisplatin) with good relief of symptoms and modest prolongation of life. A small proportion of limited small-cell lung cancer patients will be cured. In patients with extensive disease, who are incurable, single agent etoposide orally or intravenously is a possible alternative to combination chemotherapy. As in non-small-cell lung cancer, radiotherapy can provide very useful palliative relief.
urgery is the primary treatment for gastrointestinal cancer with radiotherapy sometimes being used after surgery o prevent local relapse. Chemotherapy is playing an increasingly important role.
In early-stage squamous cell carcinoma of the oesophagus surgery is the treatment of choice. In patients who are imuperable radiotherapy is given as primary treatment. More recently it has been shown that chemotherapy, comprising 5-fluorouracil and cisplatin, given concurdy rently with radiotherapy improves the cure rate and is now part of standard therapy.
STRIC CANCER AND COLONIC CANCER
Adjuvant therapy has not yet been shown to be useful in ‘gastric cancer. In contrast, in Dukes’ Band C colon canthe can the use of adjuvant chemotherapy following surgery has reduced the number of people relapsing and dying with metastatic disease by about one-third.
“In advanced metastatic gastric and colonic cancer relativly mild chemotherapy can provide good quality palliation and mprovement in quality and quantity of life in some patients. Chemotherapy is based on 5-fluorouracil and cisplatinum in gastric cancer and 5-fluorouracil and folinic acid in colonic cancer. With the appropriate support these regimens are usually very well tolerated. Ovarian cancer Surgery plays a major role in the treatment of ovarian cancer in all stages. In patients where the disease is confined to the ovary, the surgery can be curative, sometimes without the need for further therapy. In patients with more advanced disease, with spread throughout the pelvis and abdomen, surgery still has a role in improving response and survival from chemotherapy. It has been shown that the response to chemotherapy is much enhanced if the tumour is debulked to leave only small amounts of metastatic disease. The most important drugs used to treat ovarian cancer are cisplatinum and its analogue carboplatin, which is associated with less sideeffects. More recently taxol, from the bark of the Western Yew, has been shown to have substantial activity in carcinoma of the ovary.
This is the commonest cancer in young men 15-35 but comprises only 1-2% of all cancers. There are two histological types, seminomas and teratomas.
Seminomas are the least common of these tumours and are very radiosensitive. These can almost always be cured with surgery and radiotherapy to the para-aortic lymph nodes. When there is more widespread disease chemotherapy cures the majority of patients.
This disease often presents with para-aortic and pulmonary metastases. It is very rapidly growing and most patients have a raised o-fetoprotein or 13 human chorionic gonadotrophin (I3-HCG) in the peripheral blood which can be used as tumour markers to follow the response of the disease to treatment. Chemotherapy is the treatment of choice once the disease has spread and radiotherapy has very little role. The great majority of patients can be cured with chemotherapy. The major drugs used include cisplatinum, etoposide, bleomycin and ifosfamide.Management of patients with cancer of an unknown primary site Approximately 5% of all cancers present with no obvious primary site. The aim of investigation and searching for a primary is to identify turn ours that are likely to respond to treatment, and to be able to provide the most appropriate palliative care. It is also important to avoid expensive and unnecessary diagnostic procedures. The most important initial distinction is between well-differentiated and poorly differentiated carcinomas because a subset of poorly differentiated carcinomas may be extremely responsive to chemotherapy and may occasionally be cured.
The most important primaries to exclude are those that respond well to the treatment. In females breast cancer should always be considered especially if they have axillary lymphadenopathy. Even in the absence of a clinically palpable mass in the breast mammography will sometimes detect an unsuspected primary.
Ovarian cancer and thyroid cancer may also respond well to therapy and should be excluded. In men prostatic carcinoma and thyroid cancer similarly should always be considered.
With improvements in the palliative chemotherapy of advanced gastric and colonic carcinoma, younger fitter patients should also be considered for investigations of the upper and lower gastrointestinal tract to exclude these tumours.
Poorly differentiated carcinomas
In addition to the above investigations, in patients with poorly differentiated carcinomas detailed immunoperoxidase tumour staining is very important as a subgroup of these patients will turn out to have lymphoma, germ cell tumours or neuroendocrine tumours which may all be very responsive to chemotherapy.
Patients under the age of 50, particularly those with peripheral lymphadenopathy or lymph nodes in the mediastinum and retroperitoneum, may have highly responsive tumours that respond well to teratoma-type cisplatin-based chemotherapy. There are a high proportion of complete responders and a minority will achieve long-term remission.