Principles of Cancer Therapy

Successful treatment of cancer requires elimination of all cancer cells, whether at the primary site, extended to local-regional areas, or metastatic to other regions of the body. The major modalities of therapy are surgery and radiotherapy (for local and local-regional disease) and chemotherapy (for systemic sites). Other important methods include endocrine therapy (for selected cancers, eg, prostate, breast, endometrium, liver), immunotherapy (biologic response modifiers to enhance endogenous immune cell kill and tumor vaccines), and thermotherapy (cryotherapy and heat). Multimodality therapy combines the assets of each of these.

Clinical definitions of oncologic terms help clarify the goals and progress of therapy. For a potential cure, a complete remission or complete response must be achieved, which requires disappearance of clinically evident disease. Such patients may appear to be cured but may still have viable neoplastic cells that will, in time, cause relapse. A partial response is a > 50% reduction in the size of a tumor mass or masses; a partial response may lead to significant palliation and prolongation of life, but tumor regrowth is inevitable. A patient may also have no response.

The interval between disappearance of cancer and relapse is termed the disease-free interval or disease-free survival. Similarly, the duration of response is the time from partial response to the time of overt progression. Survival is the time from diagnosis to death.

Surgery
Surgery is the oldest form of effective cancer therapy. Curative surgery requires that the tumor be localized or have limited local-regional spread, which allows en bloc resection. This is particularly applicable to cancer of the bladder, breast, cervix, colon, endometrium, larynx and head and neck, kidney, lung, ovaries, and testes. In circumstances in which an en bloc resection cannot be performed, multimodality therapy with radiotherapy, chemotherapy, or chemoradiation may reduce the size of the cancer, making it amenable to surgical resection for cure.

Cancers curable with surgery alone are listed in

Table 144-1. Detailed issues about surgical treatment are discussed in sections on cancers of specific organs.

Radiotherapy
Radiotherapy can be delivered by various methods. The most common is external beam with a linear accelerator, which largely delivers photons (γ-radiation). Neutron beam radiotherapy is used for some tumors with a narrow tissue margin. Electron beam radiotherapy has a very short tissue penetration and is best used for skin or superficial cancers. Proton therapy, although limited in availability, can provide very narrow depth of field exposure with sharp margins. Brachytherapy involves placing a powerful radioactive source into the tumor bed itself (eg, in prostate or brain) via needles, thereby providing a very high dose in a small field. Systemic radioactive isotopes can be used for organs that have receptors for their uptake (thyroid cancer) or for palliation of generalized bony sites (ie, radiostrontium for metastatic prostate cancer). Curative radiotherapy generally requires local or local-regional disease that can be encompassed within the radiation field.

Radiation injury to cells is random and nonspecific, with complex effects on DNA. The efficacy of therapy depends on cellular injury beyond the normal capacity of repair. In general, repair of normal tissue is more effective than that of cancer, allowing differential cell kill.

Radiotherapy is curative in many cancers (

see Table 144-1). Radiotherapy combined with surgery (for head and neck, laryngeal, or uterine cancer) or with chemotherapy and surgery (for sarcomas or breast, esophageal, lung, or rectal cancers) improves cure rates over traditional single-modality therapy. Phototherapy, the newest multimodality approach, uses a porphyrin derivative (a protoporphyrin) to attach to and thereby illuminate the tumor for selected uptake of radiation.

Radiotherapy can provide important palliative control of cancer, even when cure is not possible. Radiotherapy for brain tumors prolongs patient functioning; for cord-compressing cancers, it can eliminate neurologic deficit; for superior vena caval syndromes, it can eliminate abrupt death; and for symptomatic or painful metastases, it usually controls symptoms.

Chemotherapy
The ideal chemotherapeutic drug would target and destroy only cancer cells without adverse effects or toxicities on normal cells. Unfortunately, no such drug exists; there is a narrow therapeutic index between cell kill of cancer cells and that of normal cells. Despite this, chemotherapy, even with single drugs, has achieved cure in selected cancers (ie, choriocarcinoma, hairy cell leukemia, chronic lymphocytic leukemia). More commonly, multidrug regimens with differing mechanisms, intracellular sites of action, and toxicities (to reduce the potential compounding of toxicity) provide significant cure rates (eg, in acute leukemia, bladder and testicular cancer, Hodgkin’s disease, malignant lymphoma, small cell lung cancer, and nasopharyngeal cancer).

The failure of chemotherapy drugs in vivo when efficacy has been documented in vitro has led to extensive studies of drug resistance. One identified mechanism, multidrug resistance, is due to several genes that limit drug dwell and function in cancer cells in the patient. Attempts to alter this resistance have not been successful.

Common effective chemotherapeutic drugs are described in

Table 144-2.

Multimodality & Adjuvant Therapy
The limited success of treatment with surgery or radiotherapy alone led to the discovery that surgery combined with radiation can increase the disease-free survival and cure rate in some tumors (eg, gynecologic, lung, laryngeal, and head and neck cancer). Because these modalities focus on local-regional control, chemotherapy is added as an adjuvant to eliminate cancer cells beyond the limited region. Adjuvant chemotherapy can increase disease-free survival and cure rate by about 30% in breast cancer in women and men, colon cancer (Dukes’ B2 and C), advanced bladder cancer, and ovarian cancer. This success has led to the use of chemotherapy or radiotherapy before surgery, termed induction (or neoadjuvant) therapy. This approach has improved survival in inflammatory and advanced breast, lung (eg, stage IIIA and B), nasopharyngeal, and bladder cancers.

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Provided by ArmMed Media
Revision date: June 22, 2011
Last revised: by Tatiana Kuznetsova, D.M.D.