Lung Cancer-2

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).

- Wobe-Mugos 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:

1)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).

2)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).

4)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).

5)Coenzyme Q10 protects the heart from damage typically caused by doxorubicin, cytoxan, and 5-fluorouracil (Wang SQ 1991).

6)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.


Integrative Cancer Therapy

Hormones. Estrogens and peptide hormones play important roles in the development and progression of lung cancer, whereas melatonin and thyroid hormones are pivotal in the stabilization and inhibition of lung cancer in men (Zhou XD et al 2002; Bhatavdekar JM et al 1994).

Estrogens: Whether produced in the body or obtained through hormone replacement therapy, estrogens may be involved in lung cancer development and progression (Inoue M et al 2006; Liu Y et al 2005). Lung cancer tissue contains an abundance of estrogen receptors, which are not found in normal lung tissue, thus opening up a possibility of antiestrogen therapy for patients with advanced lung cancer displaying estrogen receptors in their tumors (Canver CC et al 1994).

If a patient’s lung cancer displays estrogen receptors, then reducing estrogen levels in the body (because estrogen stimulates cancer growth), in addition to standard treatments, is potentially beneficial. Because body fat is a source of estrogen, it is important to establish and maintain a healthy weight (Siiteri PK 1987). In addition, the following nutritional supplements with natural antiestrogen properties show promise:

Melatonin has multiple antiestrogen actions and decreases estradiol levels in the body (Sanchez-Barcelo EJ et al 2005; Rato AG et al 1999).
Vitamin K2 (menaquinone), known for its blood coagulation effects, decreases the ratio of estradiol to estrone, slowing down estrogen activity (Otsuka M et al 2005).
Furthermore, estrogen levels in the body can be lowered by counteracting obesity (see the Obesity chapter) and keeping a low-fat diet (Deslypere JP 1995; Alavanja MC et al 1994; Kolonel LN 1993).

Peptide hormones: Peptide hormones act as growth factors and increase lung cancer growth (Moody TW 2006). For example, SCLC and NSCLC both produce gastrin-releasing peptide (GRP), neurotensin and adrenomedullin, which are growth factors, and as the name suggests, they increase lung cancer growth (Moody TW 2006). However, growth factor antagonists prevent SCLC growth in vitro and have been studied in Phase III clinical trials (Moody TW et al 2001). These growth factor antagonists may provide new treatments for SCLC patients in the future.

Melatonin: The most widely investigated anticancer hormone is melatonin (Lissoni P et al 2001). It has been used both alone and in combination with most standard cancer treatments because it improves both survival and quality of life (Lynch E 2005). Advanced lung cancer patients show a progressive reduction in melatonin levels (Mazzoccoli G et al 1999), and their daily sleep-wake patterns are disrupted (Levin RD et al 2005; Lissoni P et al 1998). However, even in patients for whom no other standard treatment is offered, melatonin with aloe vera extract stabilizes the cancer growth and improves survival (Lissoni P et al 1998).

In a study of 100 lung cancer patients who were randomized to receive either chemotherapy alone or chemotherapy with melatonin (20 mg/day orally), the five-year survival rates were significantly higher for the group of patients who received melatonin. In addition, no patient treated with chemotherapy alone was alive after two years, whereas five-year survival was achieved in three of 49 patients (6 percent) treated with chemotherapy and melatonin. Furthermore, lung cancer patients treated with melatonin tolerate chemotherapy better and have less-serious side effects (Lissoni P et al 1999, 2003a,b).

Thyroid hormones: Thyroid stimulating hormone (TSH) controls 25 percent of the body’s metabolism, thereby affecting how quickly cells (including cancer cells) grow and die. Therefore, making the thyroid underactive (a condition known as hypothyroidism) by reducing TSH levels in the body may slow down cancer growth. Hypothyroidism can be achieved artificially with the prescription drugs propylthiouracil (PTU) or Tapazole®.

When All Else Fails: Increase Survival with Hypothyroidism
A case in point: A patient originally diagnosed with metastatic lung cancer (i.e., lung cancer that had spread throughout the body) was admitted to the hospital because of a rare complication of underactive thyroid disease (i.e., hypothyroidism) called myxedema coma. This rare clinical condition can be caused by insufficient thyroid hormone (T4) replacement, infection, cold exposure, trauma, or the drug amiodarone (which causes thyroid hormone abnormalities) (Hondeghem LM 1987). The myxedema coma occurred just two months after the patient was diagnosed with metastatic lung cancer. On examination for myxedema coma, the patient was found to have no evidence of remaining cancer, and five years later the lung cancer had still not returned (i.e., he remained in remission). It was concluded that spontaneous remission (complete permanent disappearance) of the lung cancer had occurred due to a severe deficiency of thyroid hormone; in other words, thyroid hormone deprivation had induced total tumor cell death (Hercbergs A 1993, 1999).


If a lung cancer patient also has hypothyroidism or subclinical hypothyroidism, it may be wise to avoid taking too much thyroid hormone to correct this condition. By contrast, if a lung cancer patient has an overactive thyroid (hyperthyroidism), it is essential to reduce the levels of the thyroid hormones triiodothyronine (T3) and T4 to normal (or lower) as quickly as possible (typically with PTU or Tapazole®) because hypothyroidism or inadequate thyroid hormone replacement prolongs survival of lung cancer patients and in some cases causes spontaneous remission of the lung cancer (Garfield D 2002). TSH, T3, and T4 can be measured by a simple blood test.

Complementary Alternative Therapies
Vitamin and mineral supplementation is associated with longer survival and quality of life in NSCLC patients. Median survival is 4.3 years for NSCLC patients who supplement with vitamins and minerals versus 2.0 years for those who do not use such supplements (Jatoi A et al 2005a). As the statistics on conventional treatment outcomes for lung cancer remain disappointing, vitamin and mineral supplementation combined with complementary alternative therapies should be considered to help control lung cancer, maintain quality of life, and prolong survival (van Zandwijk N et al 2000). It is particularly important for advanced lung cancer patients to incorporate novel and integrative nutritional supplementation into their treatment regimens.

Vitamin D. As previously outlined in the “Surgery” section, vitamin D improves survival in early-stage NSCLC patients (Zhou W et al 2005). Therefore, vitamin D supplementation is recommended for lung cancer patients planning to undergo surgery, particularly during the winter season, and especially for those with darker skin, and for vegans who have limited sun exposure. Experimental studies show that vitamin D protects against lung cancer progression by preventing cancer spread (metastases) (Wiers KM et al 2000). Sources of vitamin D include sunlight, milk, and darkly colored fish.

Adenosine triphosphate. Adenosine triphosphate (ATP) is produced in the body and provides energy to cells. In nonrandomized studies involving advanced NSCLC patients, ATP infusions slowed weight loss and deterioration of quality of life (Haskell CM et al 1998). A randomized trial showed that ATP infusions (20–75 mg/kg per minute for 30 hours at two- to four-week intervals) have beneficial effects on weight, muscle strength, energy levels, and quality of life in patients with advanced NSCLC (Agteresch HJ et al 2003).

Intravenous ATP infusions work by restoring liver energy levels in patients with advanced lung cancer (Leij-Halfwerk S et al 2002) and by counteracting tissue loss (Agteresch HJ et al 2002). ATP is taken up by red blood cells and reaches levels 50 to 70 percent above baseline concentrations at approximately 24 hours (Agteresch HJ et al 2000). In addition, preclinical studies showed that ATP administration may improve the anticancer effects of chemotherapy (Maymon R et al 1994) and radiotherapy (Estrela JM et al 1995) and may also have protective effects against tissue damage caused by radiation (Senagore AJ et al 1992).

Green tea. A phase I clinical trial in advanced NSCLC patients determined that high doses of green tea extract (3 g/m2 daily) are well tolerated and stabilize cancer in some patients (Laurie SA et al 2005). Based on their results, the researchers proposed that green tea extract might be useful in preventing cancer progression in those at high risk for lung cancer relapse (following completion of treatment for early-stage lung cancer) or in those at high risk of developing a second cancer. In addition, green tea extract could be considered in combination with standard chemotherapy agents in advanced lung cancer (Laurie SA et al 2005).

Green tea extract can be taken safely for at least six months at an oral dose of seven to eight Japanese cups (120 mL) three times daily (Pisters KM et al 2001). The side effects of green tea extract are caffeine related. However, preclinical studies found that caffeine contributes to the prevention of tumor growth (Lu YP et al 2000; Xu Y et al 1992). Therefore, decaffeinated green tea extract may be less effective.