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Chemotherapy

Integrative Strategies To Complement Chemotherapy

Astragalus

Astragalus membranaceus has been reported to increase efficacy and reduce toxicity of several chemotherapy agents (Li 2008; Duan 2002; Zou 2003; McCulloch 2006). In a meta-analysis of studies on non-small cell lung cancer patients, astragalus-based traditional Chinese herbal formulas increased the effectiveness of platinum-based chemotherapy, reducing one-year mortality by 33% and improving tumor response, and reduced side effects (McCulloch 2006). Another meta-analysis found that Chinese herbal preparations that contained astragalus increased levels of white blood cells and reduce the the prevalence of nausea and vomiting in people undergoing chemotherapy for colorectal cancer (Taixiang 2005).

European Mistletoe Extract

European mistletoe extract (eg, Iscador) is a botanical medicine derived from the plant Viscum album and is commonly used in integrative oncology in Europe (Steele, Axtner, Happe 2014). Mistletoe extract is generally well tolerated with few serious side effects. Intravenous administration of mistletoe extract appears better tolerated than subcutaneous administration, while intratumoral injection is associated with frequent but usually mild-to-moderate side effects (Steele, Axter 2014; Mansky 2013; Steele, Axter, Happe 2014; Steele 2015).

Mistletoe extracts, including lectin-rich mistletoe extract, have been reported to induce tumor remission in single-case studies. A mouse study, using human pancreatic tumor tissue, found that lectin-rich mistletoe extract had potent antitumor activity (Rostock 2005). An uncontrolled study involving 39 patients with advanced, inoperable pancreatic cancer showed that intratumoral mistletoe injections in combination with first- and second-line chemotherapy and palliative surgery is safe (Schad 2013). Other studies have shown an improvement in quality of life in breast cancer patients treated with mistletoe while undergoing chemotherapy (Troger 2014; Eisenbraun 2011). A study in gastric cancer patients taking oral chemotherapy with a 5-FU prodrug found that those who received subcutaneous injections of mistletoe extract experienced improved quality of life compared with those who did not (Kim 2012). A randomized trial of Iscador in advanced non-small cell lung cancer patients receiving carboplatin-based chemotherapy found that those receiving Iscador were less likely to need a chemotherapy dose reduction and experienced less frequent side effects and hospitalizations (Bar-Sela 2013).

Enzymatically Modified Rice Bran

Another natural agent that has shown promise as a chemosensitizer is enzymatically modified rice bran. Preclinical studies show this compound can increase the ability of paclitaxel to kill both metastatic and non-metastatic breast cancer cells. One such study found that enzymatically modified rice bran increased the susceptibility of breast cancer cells to paclitaxel by more than 100-fold. The extract worked in synergy with paclitaxel, causing DNA damage, enhancing apoptosis, and inhibiting proliferation of metastatic breast cancer cells (Ghoneum 2014). In other laboratory studies, specially modified rice bran increased the ability of the chemotherapeutic agent daunorubicin to kill breast cancer cells (Gollapudi 2008) and promoted apoptosis in leukemia cells (Ghoneum 2003).

Enzymatically modified rice bran was also shown to complement conventional treatment of liver cancer. In a randomized controlled trial on 68 liver cancer patients, enzymatically modified rice bran was shown to improve the efficacy of common treatment approaches including chemoembolization, ethanol injection, cryoablation, and radiofrequency ablation. Thirty-eight subjects underwent interventional therapy and received one gram of rice bran extract daily for three years, while 30 underwent interventional therapy alone. Compared with interventional therapy alone, enzymatically modified rice bran in combination with interventional therapy led to reduced rates of disease recurrence (31% vs. 46%), an improved survival rate after two years (35% vs. 6.7%), and significantly reduced tumor volume (Bang 2010). Moreover, adverse side effects were less common in the group that received the rice bran extract.

Enzymatically modified rice bran has been termed a “biological response modifier” because it can modulate several aspects of immune function (Ghoneum 2011). Studies show that enzymatically modified rice bran activates natural killer cells, T cells, macrophages, and monocytes (Ghoneum 2011; Ghoneum 2004). These effects, along with an ability to stimulate endogenous free radical scavenging enzymes (Noaman 2008), may account for the potent anticancer and chemosensitizing actions of enzymatically modified rice bran extract (Ghoneum 2011; Ghoneum 2003).

Fermented Wheat Germ Extract

Fermented wheat germ extract (FWGE) is a natural product developed in Europe, where it is approved as a “dietary food for special medical purposes in cancer patients.” It is available in powder form, and has been the subject of numerous preclinical and clinical studies investigating its potential as both a direct chemotherapeutic agent as well as a complement to standard cancer radiotherapy and chemotherapy. In these capacities, this novel natural compound shows considerable promise without apparent toxicities or interference with chemotherapy efficacy. FWGE, as an addition to standard cancer treatment, has been the subject of a number of open-label trials (Boros 2005).

In one open-label trial, 21 patients with oral cancer received standard treatment, which included surgery and post-operative radiation and/or chemotherapy, while 22 patients received FWGE in addition to standard treatment. The FWGE group had significantly better outcomes compared with the control group. Local tumor recurrence and cancer progression occurred at a rate of 57.1% and 61.9%, respectively, in the control group, with corresponding rates of 4.5% and 9.1% in the FWGE group. The addition of FWGE to the standard treatment reduced the risk of cancer progression by 85% (Boros 2005).

In another open-label trial in 170 colorectal cancer patients who had previously received surgical treatment, FWGE supplementation resulted in significantly fewer progression-related events. In 66 patients who took the supplement for at least six months in addition to standard radiation and/or chemotherapy, only 3% had cancer recurrences compared with a 17.3% recurrence rate in the 104 patients who received standard treatment alone. Compared with those receiving standard treatment alone, subjects who received FWGE along with treatment also had a lower rate of new cancer metastases (7.6% vs. 23.1%), lower risk of death (12.1% vs. 31.7%), and greater chance of progression-free survival (83.3% vs. 57.7%). In this study, FWGE treatment was a stronger predictor of survival than either radiation or chemotherapy treatment (Jakab 2003).

A randomized open-label clinical trial in melanoma patients compared FWGE supplementation with dacarbazine chemotherapy. After surgery, the participants took dacarbazine alone or with FWGE (8.5 grams daily). After seven years, those receiving FWGE had longer average progression-free survival (55.8 months vs. 29.9 months) and average overall survival (66.2 months vs. 44.7 months) (Demidov 2008).

Genistein

Genistein is an isoflavone, the best-known source of which is soybeans, and widely available as a nutritional supplement (Liggins 2000; Spagnuolo 2015). A preclinical study found genistein sensitized cancer cells to the chemotherapy agent cytarabine (Shen 2007). In a cell culture study and an animal model, genistein plus cabazitaxel (Jevtana) significantly slowed the growth of metastatic castration-resistant prostate cancer more than a control solution or either alone (Zhang 2013). In a similar set of preclinical studies, genistein sensitized the diffuse large cell lymphoma subtype of non-Hodgkin lymphoma to the standard chemotherapeutic combination for this disease (cyclophosphamide, doxorubicin, vincristine, and prednisone), increasing the antitumor effect of the chemotherapy (Mohammad 2003). Genistein enhanced the cytotoxic effect of doxorubicin in HER2-positive breast cancer cells in a laboratory study, and the combination appeared to inactivate the HER2 receptor (Satoh 2003). Studies performed in prostate, breast, lung, and pancreatic cancer cells indicate genistein pretreatment may enhance cell growth inhibition and cancer cell death from cisplatin, docetaxel, and doxorubicin (Li 2005; Li 2004).

Green Tea

In an animal model of non-small cell lung cancer, treatment with cisplatin and the green tea polyphenol EGCG inhibited tumor growth more effectively than either agent alone. The authors hypothesized that EGCG might favorably modify blood supply and tumor microenvironment in non-small cell lung cancer (Deng 2013).

Cholangiocarcinoma is a type of cancer of the bile ducts that ordinarily responds poorly to chemotherapy (Lang 2009). In a mouse tumor model, oral green tea increased doxorubicin concentration in the tumor and enhanced doxorubicin’s inhibition of tumor growth 2.5-fold (Sadzuka 1998). Another study using the same mouse tumor model found that, in mice given a high dose of EGCG, there was a greater degree of tumor reduction than in mice given cisplatin. In addition, when used with cisplatin, EGCG enhanced cytotoxicity and reduced kidney toxicity (El-Mowafy 2010). Green tea polyphenols in drinking water, supplied before and after exposure to the chemotherapy drug irinotecan, protected against oxidative stress in mouse gastrointestinal tracts (Wessner 2007).

Sulforaphanes and Related Compounds

Sulfur-containing phytochemicals from broccoli and other cruciferous vegetables have shown promising complementary effects in the context of cancer chemotherapy (Jadhav 2007; Li, Zhang 2010; Conaway 2000). These compounds include glucosinolates and isothiocyanates, such as sulforaphane (Higdon 2008; Shapiro 2006).

Preclinical research has demonstrated the potential for sulfur compounds to enhance chemotherapy effectiveness. In an esophageal cancer cell line, sulforaphane decreased the expression of multidrug resistance proteins (which pump cancer drugs out of cancer cells) and increased the anticancer effects of chemotherapy drugs (Qazi 2010). In ovarian cancer, resistance to the effects of cisplatin is a major barrier to successful treatment (Hunakova 2014). In a laboratory study, cisplatin-sensitive and cisplatin-resistant ovarian cancer cells were exposed to cisplatin, cisplatin plus EGCG from green tea, or cisplatin plus sulforaphane; both sulforaphane and EGCG increased cisplatin-induced cell death and interruption of cell division (Chen, Landen 2013). A watercress-derived isothiocyanate successfully sensitized cervical cancer cells to cisplatin, enhancing cancer cell death (Wang 2011). In a rodent model of breast cancer, daily injections of sulforaphane reduced cancer stem cells and down-regulated cancer cell self-renewal signaling pathways (Li, Zhang 2010).

Sulforaphane may also have a role in protecting healthy cells from toxic damage due to cancer treatment. Sulforaphane reduced signs of DNA damage in cultured white blood cells exposed to radiation, as well as doxorubicin and bleomycin (Blenoxane) (Katoch 2013), suggesting it may protect healthy cells against chemotherapy-induced toxicity. A rodent study showed that pretreatment with sulforaphane diminished cisplatin-induced oxidative damage to the liver and preserved mitochondrial function (Gaona-Gaona 2011).

Ashwagandha (Withania somnifera)

Ashwagandha may reduce the side effects of cyclophosphamide, paclitaxel, and doxorubicin without diminishing the anticancer actions of these drugs. In animal models, ashwagandha improved white blood cell and bone marrow response, reduced toxic damage to healthy tissues, and preserved organ function in animals treated with these chemotherapy agents. Ashwagandha also reduced proliferation of tumor cells while increasing survival time of the animals (Winters 2006). In one study, tumor-bearing mice that received ashwagandha root exhibited reductions in tumor cell counts and tumor weight, as well as a 27.5% increase in lifespan, compared with tumor-bearing mice that did not receive ashwagandha (Winters 2006).

Table 4: Selected Integrative Interventions and Their Influence on Chemotherapy Outcomes in Human Studies

Drug Class

Drug

Natural Agents Shown to Improve Outcomes in Combination with Chemotherapy

Human Data

Alkylating agents

Cyclophosphamide

European Mistletoe Extract (Viscum album)

Tröger 2014 Treatment with mistletoe extract in addition to cyclophosphamide, doxorubicin, and 5-FU led to better quality of life in patients with breast cancer than cyclophosphamide, doxorubicin, and 5-FU without mistletoe extract.

Carbazilquinone

Polysaccharide K (PSK)

Kondo 1991 – Treatment with PSK plus carbazilquinone following curative surgery increased survival compared with carbazilquinone alone in patients with moderately advanced (stage 1 or 2) gastric carcinoma.

Carboplatin

Eicosapentaenoic acid (EPA)/Docosahexaenoic acid (DHA)

Murphy 2011 – Treatment with fish oil (EPA + DHA) along with carboplatin and vinorelbine or gemcitabine increased response rate (defined as complete plus partial response to chemotherapy) compared with chemotherapy alone in patients with non-small cell lung cancer. However, there was no significant between-group difference in 1-year survival.

European Mistletoe Extract

Bar-Sela 2013 A randomized trial of mistletoe extract in advanced non-small cell lung cancer patients receiving carboplatin-based treatment found those receiving mistletoe extract were able to reduce their chemotherapy dose and experienced less frequent severe non-hematological side effects and hospitalizations.

Cisplatin

Astragalus

Guo 2012 – No improvement in overall survival or tumor regression was observed for patients with non-small cell lung cancer treated with injections of astragalus polysaccharide along with cisplatin and vinorelbine. However, patients showed improvement in quality of life compared with those receiving cisplatin and vinorelbine without astragalus.

Zou 2003 – Prolonged average length of remission, increased median survival period, and improved quality of life were observed for patients with non-small cell lung cancer treated with astragalus injection along with mitomycin-C, vinblastine, and cisplatin compared with chemotherapy alone.

McCulloch 2006 Meta-analysis investigating astragalus-based Chinese herbal medicine preparations in combination with platinum-based chemotherapy compared with platinum-based chemotherapy alone in patients with advanced non-small cell lung cancer. Findings in favor of astragalus included 33% reduced risk of death at 12 months (12 studies) and 34% improved tumor-response rate (30 studies).

Ginseng

Chen 2009 – Treatment with intravenous Shengmai injection (consisting of red ginseng, lilyturf root, and magnolia vine fruit) and oral Gujin granule (consisting of milkvetch root, asiabell root, mulberry bark, lilyturf root, balloon flower root, magnolia vine fruit, and licorice root) along with vinorelbine and cisplatin chemotherapy increased response rate and median survival time compared with chemotherapy alone in patients with non-small cell lung cancer. However, there was no between-group difference in 1-year survival or median time to progression.

Huang 2009 – Treatment with Shenyi Capsule (which contained ginsenoside Rg3) along with chemotherapy consisting of gemcitabine plus cisplatin improved quality of life and 1-year survival rate, but did not significantly improve total response rate compared with chemotherapy alone in patients with advanced esophageal cancer.

Melatonin

Lissoni 2007 – Treatment with melatonin plus cisplatin and etoposide increased the percentage of patients with non-small cell lung cancer who achieved complete response or partial response compared with chemotherapy alone.

Lissoni 2003 – Treatment with melatonin plus cisplatin and etoposide increased 5-year survival rate in patients with metastatic non-small cell lung cancer compared with chemotherapy alone.

Lissoni 1999 – Treatment with melatonin plus cisplatin plus etoposide or gemcitabine alone increased the percentage of patients with lung cancer who achieved complete response or partial response, as well as the percentage of patients who survived for one year, compared with chemotherapy alone. Also, melatonin plus 5-FU and cisplatin increased 1-year survival rate compared with 5-FU plus cisplatin without melatonin in patients with head and neck cancers.

Lissoni 1997 – Treatment with melatonin plus cisplatin and etoposide increased tumor response rate (defined as partial response plus complete response) compared with chemotherapy alone in patients with non-small cell lung cancer.

PSK

Nishiwaki 1990 – Treatment with PSK plus cisplatin and vindesine increased response rate compared with cisplatin and vindesine alone in patients with stage III but not stage IV lung cancer.

Dacarbazine

Fermented Wheat Germ Extract (FWGE)

Demidov 2008 – A randomized, early-stage, open-label clinical trial in melanoma patients examined the effect of up to one year of FWGE supplementation added to dacarbazine adjuvant chemotherapy compared with dacarbazine alone. After seven years, mean progression-free survival was 55.8 months in the treatment group and 29.9 months in the control group. Mean overall survival in the treatment group was 66.2 months and 44.7 months in the control group. The dosage of FWGE in this study was 8.5 grams, once daily, taken continuously for up to 12 months.

Oxaliplatin

Melatonin

Lissoni 2007 – Treatment with melatonin plus oxaliplatin and 5-FU/folinic acid increased the percentage of patients with colorectal cancer who achieved complete response or partial response compared with chemotherapy alone.

Antimetabolites

Doxifluridine (5-FU prodrug)

European Mistletoe Extract

Kim 2012 In gastric cancer patients who had undergone surgery, treatment with mistletoe extract plus doxifluridine led to better global health status and quality of life than doxifluridine alone.

5-Fluorouracil (5-FU)

Melatonin

Lissoni 2007 – Treatment with melatonin plus oxaliplatin and 5-FU/folinic acid increased the percentage of patients with colorectal cancer who achieved complete response or partial response compared with chemotherapy alone.

Yan 2002 – Treatment with melatonin plus transcatheter arterial chemoembolization (TACE) using mitomycin-C, doxorubicin, and 5-FU increased effective rates as well as 6-month, 1-year, and 2-year survival in patients with advanced primary hepatocellular carcinoma compared with TACE alone.

Lissoni 1999 – Treatment with melatonin plus 5-FU and folinic acid increased the percentage of patients with gastrointestinal tumors who achieved complete response or partial response compared with chemotherapy alone. Also, melatonin plus 5-FU and cisplatin increased 1-year survival rate compared with 5-FU plus cisplatin alone in patients with head and neck cancers.

PSK

Takahashi 2005 – Treatment with PSK plus 5-FU increased 7-year overall survival and 7-year disease-free survival compared with 5-FU alone in patients with colorectal cancer.

Ito 2004 – Treatment with PSK plus 5-FU improved rate of cancer-related mortality but not 7-year disease-free survival or overall survival compared with 5-FU alone in patients with colon cancer.

Nakazato 1994 – Administering PSK plus mitomycin and 5-FU following curative gastrectomy improved 5-year survival and 5-year disease-free survival rates compared with mitomycin and 5-FU alone in patients with gastric cancer.

Mitomi 1992 – Administering PSK plus mitomycin-C and 5-FU following curative resection improved disease-free survival and overall survival compared with mitomycin-C and 5-FU alone in patients with colorectal cancer.

Nakazato 1989 – Treatment with PSK plus 5-FU following radical gastrectomy increased disease-free survival and overall survival compared with 5-FU alone in patients with gastric cancer.

Mitomi 1989 – Administering PSK plus mitomycin-C and 5-FU following curative resection improved disease-free survival and overall survival compared with mitomycin-C and 5-FU alone in patients with colorectal cancer.

Futraful

PSK

Toge 2000 – Treatment with PSK plus mitomycin-C and futraful following macroscopically curative resection improved 5-year survival rate compared with mitomycin-C and futraful alone in patients with gastric cancer who had a preoperative granulocyte and lymphocyte count ratio of at least 2.0.

Niimoto 1988 – Treatment with PSK plus mitomycin-C and futraful following curative surgery increased 5-year survival rate compared with mitomycin-C and futraful alone in patients with gastric cancer.

Gemcitabine

EPA/DHA

Murphy 2011 – Treatment with fish oil (EPA + DHA) along with carboplatin and vinorelbine or gemcitabine increased response rate (defined as complete plus partial response to chemotherapy) compared with chemotherapy alone in patients with non-small cell lung cancer, but there was no significant between-group difference in 1-year survival.

Ginseng

Huang 2009 – Treatment with Shenyi Capsule (which contained ginsenoside Rg3) along with chemotherapy consisting of gemcitabine plus cisplatin improved quality of life and 1-year survival rate but did not improve total response rate compared with chemotherapy alone in patients with advanced esophageal cancer.

Melatonin

Lissoni 1999 – Treatment with melatonin plus gemcitabine increased 1-year survival compared with gemcitabine alone in patients with lung cancer.

Tegafur-Uracil (UFT)

PSK

Totsuka 2013 – Treatment with PSK plus UFT improved 5-year survival compared with UFT alone in patients with colorectal cancer who had a low preoperative lymphocyte ratio.

Akagi 2010 – Treatment with PSK plus UFT improved overall survival compared with UFT alone in patients with gastric cancer.

Ohwada 2004 – Treatment with PSK plus UFT and mitomycin-C improved 5-year disease-free survival compared with UFT and mitomycin-C in patients with stage II or III colorectal cancer and increased overall survival in patients with stage III colorectal cancer.

Ohwada 2003 – Treatment with PSK plus UFT and mitomycin improved 3-year disease-free survival compared with UFT and mitomycin alone in patients with stage II or III colorectal cancer. Also, PSK plus UFT and mitomycin improved 3-year overall survival and prevented distant metastases compared with UFT and mitomycin alone in patients with stage III colorectal cancer

Antitumor antibiotics

Doxorubicin

Melatonin

Yan 2002 – Treatment with melatonin plus TACE using mitomycin-C, doxorubicin, and 5-FU increased effective rates as well as 6-month, 1-year, and 2-year survival in patients with advanced primary hepatocellular carcinoma compared with TACE alone.

Melatonin

Lissoni 1999 – Treatment with melatonin and doxorubicin increased the percentage of breast cancer patients who achieved complete or partial response and the percentage of patients who survived for one year compared with chemotherapy alone.

Mitomycin-C

Astragalus

Zou 2003 – Increased effective rate, prolonged remission rate, increased overall survival, and improved quality of life were observed for patients with non-small cell lung cancer treated with astragalus injection along with mitomycin-C, vinblastine, and cisplatin compared with chemotherapy alone.

Melatonin

Yan 2002 – Treatment with melatonin plus TACE using mitomycin-C, doxorubicin, and 5-FU increased effective rates as well as 6-month, 1-year, and 2-year survival in patients with advanced primary hepatocellular carcinoma compared with TACE alone.

PSK

Ohwada 2004 – Treatment with PSK plus UFT and mitomycin-C improved 5-year disease-free survival compared with UFT and mitomycin-C in patients with stage II or III colorectal cancer and increased overall survival in patients with stage III colorectal cancer.

Ohwada 2003 – Treatment with PSK plus UFT and mitomycin improved 3-year disease-free survival compared with UFT and mitomycin alone in patients with stage II or III colorectal cancer. Also, PSK plus UFT and mitomycin improved 3-year overall survival and prevented distant metastases compared with UFT and mitomycin alone in patients with stage III colorectal cancer.

Toge 2000 – Treatment with PSK plus mitomycin-C and futraful following macroscopically curative resection improved 5-year survival rate compared with mitomycin-C and futraful alone in patients with gastric cancer who had a preoperative granulocyte and lymphocyte count ratio of at least 2.0.

Nakazato 1994 – Administering PSK plus mitomycin and 5-FU following curative gastrectomy improved 5-year survival and 5-year disease-free rates compared with mitomycin and 5-FU alone in patients with gastric cancer.

Mitomi 1992 – Administering PSK plus mitomycin-C and 5-FU following curative resection improved disease-free survival and overall survival compared with mitomycin-C and 5-FU alone in patients with colorectal cancer.

Niimoto 1988 – Treatment with PSK plus mitomycin-C and futraful following curative surgery increased 5-year survival and overall survival rate compared with mitomycin-C and futraful alone in patients with gastric cancer.

Camptothecin analogues

Irinotecan

Melatonin

Cerea 2003 – Treatment with melatonin plus irinotecan increased disease control (defined as partial response plus stable disease) in patients with metastatic colorectal cancer compared with irinotecan alone.

Cytokines

Interleukin-2 (IL-2)

Melatonin

Barni 1995 – Treatment with low-dose IL-2 plus melatonin increased 1-year survival rate compared with supportive care in patients with metastatic colorectal cancer.

Lissoni 1995 – Treatment with melatonin plus low-dose IL-2 increased 1-year survival and improved performance status compared with supportive care in patients with metastatic solid tumors.

Lissoni, Meregalli 1994 – Treatment with melatonin plus low-dose IL-2 increased 1-year survival rate compared with cisplatin plus etoposide in patients with advanced non-small cell lung cancer.

Lissoni, Barni 1994 – Treatment with melatonin plus low-dose IL-2 increased response rate and 1-year survival rate compared with IL-2 alone in patients with locally advanced or metastatic solid tumors.

Protein kinase inhibitors

Imatinib

Curcumin

Ghalaut 2012 – Treatment with curcumin-containing turmeric powder plus imatinib decreased nitric oxide levels compared with imatinib alone in patients with leukemia. Increased nitric oxide levels have been associated with different leukemias.

Taxanes

Docetaxel

Vitamin D3

Beer 2007 – Treatment with docetaxel plus high-dose calcitriol improved survival compared with docetaxel alone in patients with metastatic androgen-independent prostate cancer.

Paclitaxel

Melatonin

Lissoni 1999 – Treatment with melatonin plus paclitaxel increased 1-year survival compared with paclitaxel alone in patients with breast cancer.

Topoisomerase inhibitors

Etoposide

Melatonin

Lissoni 2007 – Treatment with melatonin plus cisplatin and etoposide increased the percentage of patients with non-small cell lung cancer who achieved complete response or partial response compared with chemotherapy alone.

Lissoni 2003 – Treatment with melatonin plus cisplatin and etoposide increased 5-year survival rate in patients with metastatic non-small cell lung cancer compared with chemotherapy alone.

Lissoni 1999 – Treatment with melatonin plus cisplatin and etoposide increased the percentage of patients with lung cancer who achieved complete response or partial response, as well as the percentage of patients who survived for one year, compared with chemotherapy alone.

Lissoni 1997 – Treatment with melatonin plus cisplatin and etoposide increased the tumor response rate (partial response plus complete response) compared with chemotherapy alone in patients with non-small cell lung cancer.

Vinca Alkaloids

Vinblastine

Astragalus

Zou 2003 – Prolonged median remission time, increased median survival period, and improved quality of life were observed for patients with non-small cell lung cancer treated with astragalus injection along with mitomycin-C, vinblastine, and cisplatin compared with those treated with chemotherapy alone.

Vindesine

PSK

Nishiwaki 1990 – PSK plus cisplatin and vindesine increased response rate compared with cisplatin and videsine alone in patients with stage III but not stage IV lung cancer.

Vinorelbine

Astragalus

Guo 2012 – No improvement in overall survival was observed for patients with non-small cell lung cancer treated with injections of astragalus polysaccharide along with cisplatin and vinorelbine. However, patients showed improvement in quality of life compared with those receiving cisplatin and vinorelbine alone.

EPA/DHA

Murphy 2011 – Treatment with fish oil (EPA + DHA) along with carboplatin and vinorelbine or gemcitabine increased response rate (defined as complete plus partial response to chemotherapy) compared with chemotherapy alone in patients with non-small cell lung cancer, but there was no significant between-group difference in 1-year survival.

Ginseng

Chen 2009 – Treatment with intravenous Shengmai injection (consisting of red ginseng, lilyturf root, and magnolia vine fruit) and oral Gujin granule (consisting of milkvetch root, asiabell root, mulberry bark, lilyturf root, balloon flower root, magnolia vine fruit, and licorice root) along with navelbine and cisplatin chemotherapy increased response rate and median survival time compared with chemotherapy alone in patients with non-small cell lung cancer. However, there was no significant between-group difference in 1-year survival or median time to progression.

Clinical Trials

Cancer patients undergoing chemotherapy may wish to consider participating in a clinical trial, particularly if their type of cancer is known to be resistant or refractory to chemotherapy. ClinicalTrials.gov is an excellent and easy-to-use resource for ongoing and planned chemotherapy clinical trials. For example, if one is interested in a particular therapy, such as “hyperthermia,” a search of the clinicaltrials.gov database (“hyperthermia” AND “cancer”) will show all clinical trials studying hyperthermia in the context of cancer. Alternatively, simply entering the name or type of cancer (eg, “glioblastoma”) will show all of the clinical trials evaluating various treatments for that particular type of cancer.

Note: this protocol should be consulted in conjunction with Cancer Treatment: The Critical Factors. Other protocols potentially of interest include Cancer Radiation Therapy, Cancer Surgery, Cancer Adjuvant Therapy, Complementary Alternative Cancer Therapies, and Cancer Vaccines and Immunotherapy.


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