How is Lung Cancer Treated?
Treatment methods depend on the type of lung cancer. SCLCs are treated with chemotherapy with or without radiotherapy, as surgery is unlikely to control the cancer in most cases. NSCLCs, if contained within the lung area, may be cured with either surgery or radiotherapy. Alternatively, certain chemotherapy agents are beneficial in specific cases.
Surgery. The goal of surgery is to remove as much of the cancer as possible in order to prevent a recurrence, to increase the effectiveness of chemotherapy and radiotherapy if they are needed, and to use the cancer cells to make a vaccine if required.
SCLC: Approximately 25 percent of SCLC patients with a single lung nodule (i.e., limited disease) can be cured with surgery (Chandra V et al 2006; Raez L et al 2005). The five-year survival rate of stage I patients with a peripherally located tumor who undergo cancer surgery is 44.9 percent, compared with 11.3 percent for conventionally treated patients (i.e., those treated with chemotherapy or chemoradiotherapy) (Rostad H et al 2004). However, studies show surgery will not benefit most SCLC patients (Waddell TK et al 2004).
Complete lung (pulmonary) function tests should be performed before surgery because part of a lung lobe or an entire lung may be removed. The chapter titled Cancer Surgery provides information on nutritional supplementation in preparation for surgery and for recuperation afterwards.
NSCLC: Fewer than 25 percent of patients with NSCLC are diagnosed with early-stage disease and are best treated by surgery (Scagliotti GV et al 2003). The five-year survival rate of NSCLC patients who undergo complete removal of cancer via surgery is 33 percent (Nesbitt JC et al 1995).
The combined effects of the season in which surgery is performed and recent vitamin D intake are associated with the survival of early-stage NSCLC patients. Some 56 percent of NSCLC patients who have surgery during summer and have the highest vitamin D intake (from sunlight) have remissions lasting more than five years, compared with 23 percent of patients who have surgery during winter and have the lowest vitamin D intake (Zhou W et al 2005). Therefore, if regular exposure of the skin to sunlight (which makes vitamin D in the body) is not possible before cancer surgery, then increased vitamin D intake or supplementation is suggested as an alternative.
Surgical removal of lung cancer causes a significant reduction of total plasma antioxidant capacity in lung cancer patients during the first postoperative day (Erhola M et al 1998). An antioxidant-rich diet is therefore recommended after surgery.
If cancer returns after surgery, it usually occurs within two years and involves cancer spread to the brain, bones, and liver. Treatments after surgery, such as chemotherapy or radiotherapy (or both), have been tested, but unfortunately they generally do not improve survival rates for most advanced lung cancer patients (Scagliotti GV et al 2003).
Radiation therapy (radiotherapy). The goal of radiotherapy is to kill any cancer cells remaining after surgery and to cure patients with early-stage lung cancer if they are not suitable for surgery or if they refuse it. It is also used to relieve symptoms in advanced cancer patients (Silvano G 2006).
In the past, radiotherapy after surgery had an unfavorable effect on survival. A meta-analysis found that the risk of death increased by 21 percent and the two-year survival rate fell seven points (from 55 to 48 percent) with radiation therapy after surgery (PORT Meta-analysis Trialists Group 1998). However, in those studies most of the patients were treated with older technology (cobalt-60) (Machtay M et al 2001). The newer radiotherapy technologies, such as intensity modulated radiotherapy, four-dimensional proton beam therapy, image guided radiotherapy, three-dimensional conformal radiotherapy, and radiation seeds (brachytherapy), reduce lung and heart damage (e.g., pneumonitis and fibrosis) significantly and, when combined with nutritional supplements, improve overall survival (Chang JY et al 2006; Engelsman M et al 2006; Fanta J et al 2006; Keall P et al 2006; Nagata Y et al 2006; Silvano G 2006; Mehta V 2005).
SCLC: Radiation therapy to the chest area is used to treat SCLC that has spread to bone and the central nervous system, and it improves survival in patients with limited-stage disease but not those with widespread disease. Whole-brain radiation therapy decreases the occurrence of cancer spread to the central nervous system but does not affect survival (Wagner H Jr 1997).
NSCLC: Radiation therapy combined with alpha-tocopherol (a type of vitamin E) and pentoxifylline (Trental®) improves survival in stage IIIB NSCLC (Engelsman M et al 2006; Misirlioglu CH et al 2006; Silvano G 2006): 66 patients were treated with alpha-tocopherol (300 mg twice daily) and Trental® (400 mg three times daily) during radiotherapy, followed by 300 mg alpha-tocopherol and 400 mg Trental® daily for three months after radiotherapy. In patients who received Trental® and alpha-tocopherol, one- and two-year overall survival rates were 55 percent and 30 percent, respectively, and most patients survived at least 18 months. In patients treated with radiotherapy alone, one- and two-year overall survival rates were significantly lower, 40 percent and 14 percent, respectively, with a median survival of 10 months (Misirlioglu CH et al 2006). Trental® is safe and effective in preventing lung damage caused by radiotherapy (Mehta V 2005).
Several nutritional supplements may also mitigate the effects of radiotherapy.
- Coenzyme Q10 and vitamin E have protective effects against heart damage (cardiotoxicity) caused by radiation (Wang SQ 1991).
- Proteolytic enzymes were given systemically to 44 patients with lung cancer undergoing radiation treatment (and polychemotherapy), It prevented lung damage, specifically fibrosis (Smolanka II 2000).
See the chapter titled Cancer Radiation Therapy for information on other nutritional supplements (taurine, L-arginine, and vitamin A) that help radiotherapy kill cancer cells without damaging normal, healthy cells or causing heart or lung damage or other side effects, thus improving the success of radiotherapy for lung cancer. Cancer Radiation Therapy also provides a list of proton beam therapy centers in North America.
Chemotherapy. The goal of chemotherapy is to treat lung cancer with drugs that have a specific toxic effect on cancer cells and result in direct cancer death. It is sometimes used before surgery to shrink inoperable tumors to make them operable. In these cases the response rates vary from 50 to 60 percent.
Unfortunately, chemotherapy cannot selectively destroy cancer cells; it damages healthy cells too, resulting in many serious and often life-threatening side effects (such as low blood cell counts, immunosuppression, and heart damage). The chapter titled Cancer Chemotherapy outlines nutritional supplements and prescription drugs that mitigate the well-known adverse effects of specific chemotherapy drugs.
NSCLC: In patients with early-stage NSCLC completely removed by surgery, cisplatin plus Navelbine therapy after surgery (without radiotherapy) significantly prolonged survival (94 versus 73 months) compared with surgery alone, but not without severe toxicities (low white blood cell counts, nausea, vomiting, and fatigue) and two deaths among 242 patients. The five-year survival rates were 69 percent and 54 percent, respectively (Winton T et al 2005). By contrast, chemotherapy with alkylating agents (mainly cyclophosphamide or nitrosourea in combination with methotrexate) after surgery is detrimental to survival (producing a 15 percent increased risk of death) and should not be used to treat NSCLC after surgery. Furthermore, the use of radiotherapy in combination with chemotherapy after surgery is not recommended as a treatment for patients with completely removed NSCLC (Alam N et al 2006).
SCLC: A customized chemotherapy approach including chemosensitivity testing (see the Cancer Chemotherapy chapter) is critical to determine which chemotherapy combinations will be effective in killing these cancers, particularly in early-stage SCLC. Tailoring chemotherapy to the unique characteristics of patients and their tumor should improve treatment outcome, provided that patients are in fairly good health (Huang CL et al 2006). The chemotherapy drugs cisplatin and etoposide, or oral topotecan (Hycamtin®) with intravenous cisplatin, are used to treat SCLC, resulting in one- and two-year survival rates of 31 percent and 5 to 20 percent, respectively, depending on the stage of the cancer (Eckardt JR et al 2006).
The following supplements may optimize the effects of chemotherapy:
- Polysaccharopeptide (PSP), from the mushroom Coriolus versicolor, helps lessen symptoms and prevents decline in immune status of lung cancer patients who are undergoing chemotherapy or radiotherapy (Ng TB 1998).
- Low molecular weight heparin, an anticoagulant, improves survival in patients with SCLC undergoing chemotherapy with Cytoxan®, Ellence® (epirubicin), and Oncovin® (vincristine). Median overall survival was eight months with chemotherapy alone and 13 months when low molecular weight heparin was added to chemotherapy (Altinbas M et al 2004).
- Scutellaria baicalensis is used in traditional Chinese medicine and increases blood cell production during chemotherapy (when it is typically reduced, resulting in side effects). It also intensifies bone-marrow activity (erythro- and granulocytopoiesis) and the numbers of circulating red and white blood cell precursors (Udut EV et al 2005; Gol’dberg VE et al 1997). Lung cancer patients who took Scutellaria baicalensis extract during chemotherapy had a beneficial increase in the number of immunoglobulins and maintained their relative number of T cells (Gol’dberg VE et al 1997).
- Coenzyme Q10 protects the heart from damage typically caused by doxorubicin, cytoxan, and 5-fluorouracil (Wang SQ 1991).
- A clinical study tested the efficacy of high-dose multiple antioxidants (ascorbic acid, 6100 mg daily; dl-alpha-tocopherol (vitamin E), 1050 mg daily; and beta-carotene, 60 mg daily) in addition to chemotherapy (Taxol® and carboplatin) in 136 advanced NSCLC patients. The overall survival rates at one year in the chemotherapy-alone group were 32.9 percent and in the antioxidants-plus-chemotherapy group, 39.1 percent. At two years, the two groups’ survival rates were 11.1 percent and 15.6 percent, respectively (Pathak AK et al 2005).
Hormones and chemotherapy. Advanced stage NSCLC patients who have had no previous surgery or chemoradiotherapy may benefit from a combination of hormones and oral chemotherapy. Treatment with melatonin, vitamin D, retinoids, somatostatin, bromocriptine, and the chemotherapy drug Cytoxan® improved survival and quality of life (relieved cough, shortness of breath, pain, fatigue, and insomnia) in NSCLC patients. Median survival time was 12.9 months (range, 1.5–33.5 months), and the overall survival rates at one and two years were 51.2 percent and 21.1 percent, respectively (Norsa A et al 2006).
Customizing Chemotherapy to the Patient
The concept of customized chemotherapy involves predicting how well proposed chemotherapy drugs will kill a patient’s cancer or lower the patient’s risk of adverse effects (Von Hoff DD 1990) before they are given to the patient. It is critical to extending survival time (Thunnissen FB et al 2006). Molecular markers in patients’ tumors can help predict response to specific chemotherapy drugs.
- Iressa® treatment is linked with favorable survival in NSCLC patients whose tumors have low levels of ribonucleotide reductase (Huang CL et al 2006; Kwon WS et al 2006).
- The ability of 5-fluorouracil to kill lung cancer cells depends on the activity of dihydropyrimidine dehydrogenase and thymidylate synthase in patients’ tumors (Ploylearmsaeng SA et al 2006; Takizawa M et al 2006).
- The responsiveness of NSCLC to Iressa® and Tarceva® depends on the presence of epidermal growth factor receptor (EGFR) mutations in the tumor (Tokumo M et al 2006).
- The response to Taxol® and Navelbine® depends on tubulin III and stathmin mRNA levels in tumor cells. High levels of tubulin III are associated with a poor response to chemotherapy and a shorter progression-free survival (Seve P et al 2005).
- If the tumor shows BRCA1 and ERCC1 (genes involved in DNA repair pathways), then cisplatin, carboplatin, and taxanes will not be effective in killing the tumor, resulting in poor survival (Rosell R et al 2006; Santarpia M et al 2006).
For more details, see Cancer Chemotherapy: Evaluating the Molecular Biology of the Tumor Cell Population and Chemosensitivity Testing.