Explanation of First-line and Second-line Chemotherapy Regimens

First line therapy is the treatment regimen or regimens that are generally accepted by the medical establishment for initial treatment of a given type and stage of cancer. It is also called primary treatment or therapy.  The intent of first-line therapy is to cure the cancer if possible.  Also called induction therapy, this primary therapy is the first assault of chemotherapy drugs on the malignancy.

The US government’s Agency for Healthcare Research and Quality operates a clearinghouse of evidence-based clinical practice guidelines as do other organizations – both governmental and non-governmental around the world.  As new evidence becomes available, the consensus on a first-line treatment for a given cancer may change.  Cancer treatments are subject to more variation than the treatments for most diseases. This is especially true for cancers with low survival rates.

How are these guidelines written?  They name the one or more chemotherapy drugs (e.g. cisplatin and paclitaxel), dosages, timing of dosage (e.g every third day), mode of administration (e.g. intravenous), and length of treatment (e.g. 6 weeks).

The written guidelines and the unwritten practices of the community of oncologists are the closest thing to a standard of treatment. First-line therapies for cancers are usually one or a combination of: radiation, surgery, and chemotherapy. There are different types of these treatment modalities. Variations and tweaks to the therapy regimens may be employed as the doctor takes into account the patient’s age, general health, other diseases, and stage of cancer.

There is no law, or even a community of practice rule, that doctors must use the accepted first-line therapy for a patient, although when they do they “cover their backsides” to some extent and reduce their exposure to malpractice suits.

Second-line therapies are those tried when the first ones do not work adequately. The management of a cancer case requires regular evaluation of treatment and adjustment as needed. A break with the primary treatment and an adoption of a new regimen signals “second-line treatment.” The first-line therapy may not have worked, may have had some limited efficacy, or may have produced unacceptable side effects, damaged organs in the body, or jeopardized the patient’s life. Sometimes first-line therapies show progress for a period of time followed by a stalling or continued growth of the cancer.

Often the FDA will specifically approve a new drug for second-line therapy. This labeling is common for new drugs that treat cancers which already have accepted treatments. The idea is that if the older drugs and regimens used don’t work, there is less to lose by using the new drug. After years of experience and many patients treated with the new drug, the manufacturer may ask the FDA to expand the labeling to include first-line treatment and/or treatment on other forms of cancer.

Of course, oncologists still have the freedom to use these drugs for first-line treatment also; the drugs are just “labeled” for second-line treatment, and some insurance companies may not pay for them when used as first-line.

The terms “third-line therapy” and even “fourth-line therapy” are occasionally used for subsequent treatment, but salvage therapy is also used. Written guidelines rarely specify anything beyond second-line therapy. The same treatments can be used for subsequent treatment. “Third-line therapy” and such are used mostly in academic writing.


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