Background/Aim: The acidic tumor microenvironment is associated both with the progression and drug resistance of cancer. We aimed to investigate the effects of alkalization therapy performed concurrently with chemotherapy on the survival of advanced pancreatic cancer patients (study registration: UMIN 000035659). Patients and Methods: Twenty-eight patients with metastatic or recurrent pancreatic cancer were assessed in this study. Alkalization therapy consisted of an alkaline diet with supplementary oral sodium bicarbonate (3.0-5.0 g/day). Results: The mean urine pH was significantly higher after the alkalization therapy (6.85±0.74 vs. 6.39±0.92; p7.0) was significantly longer than those with low urine pH (≤ 7.0) (16.1 vs. 4.7 months; p<0.05). Conclusion: An alkalization therapy may be associated with better outcomes in advanced pancreatic cancer patients treated with chemotherapy.

One of the most unique characteristics of cancer metabolism is activated aerobic glycolysis, which is called the “Warburg effect”, and is a hallmark of cancer. An acidic tumor microenvironment (TME) resulting from activated anaerobic glycolysis is associated with cancer progression, multi-drug resistance, and immune escape. Several in vitro and in vivo studies reported that neutralization of the acidic TME by alkalizing agents, such as bicarbonate, resulted in the suppression of cancer progression and a potential benefit for anti-cancer drug responses. In clinical settings, alkalizing effects were achieved not only by alkalizing agents, but also by a following a particular diet. An epidemiological study demonstrated that more fruits and vegetables and less meat and dairy products are associated with an increase in urine pH, which may reflect the alkalizing effect on the body. However, it remains unclear whether alkaline dietary intervention improves the effects of cancer treatment. Moreover, there are few clinical reports to date regarding cancer treatments being performed on patients together with alkalization therapy. In this review, we investigated whether alkalization therapy, which includes an alkaline diet and/or alkalizing agents, improves cancer treatment.

Background/Aim: This study aimed to investigate the effects of the combination of alkalization therapy (an alkaline diet and bicarbonate therapy) and intravenous vitamin C treatment on chemotherapy outcomes in patients with small-cell lung cancer (SCLC) (study registration: UMIN000043056). Patients and Methods: Twelve patients with SCLC in the intervention group (receiving both alkalization therapy and vitamin C treatment together with chemotherapy) were retrospectively compared to 15 patients with SCLC in the control group (receiving chemotherapy only). Results: The mean urine pH of the intervention group was significantly higher than that of the control group (7.32±0.45 vs. 6.44±0.74, respectively; p<0.005). The median overall survival for the intervention group was 44.2 months (95% confidence interval=22.0−not reached), as compared with 17.7 months for the control group (95% confidence intervaI=13.5−not reached; p<0.05). Conclusion: The combination of alkalization therapy and intravenous vitamin C treatment may be associated with favorable outcomes in patients with SCLC receiving chemotherapy.

Neutralization of the acidic tumor microenvironment, which is associated with both progression and drug resistance of cancer cells, may be a new treatment option for progressing forms of cancer. We conducted a case-control study to investigate the effects of alkalization therapy, consisting of an alkaline diet with supplementary oral sodium bicarbonate, in patients with metastatic or recurrent pancreatic cancer (study registration no.: UMIN000036126). Thirty-six patients in the alkalization group (Karasuma Wada Clinic; alkalization therapy plus chemotherapy) were retrospectively compared to 89 patients in the control group (Kyoto University Hospital; chemotherapy only). The median overall survival (OS) in the alkalization group was significantly longer than that in the control group (15.4 vs. 10.8 months; p7.0 or ΔpH>1.0) in the alkalization group was significantly longer than that of the control group. Alkalization therapy may enhance the effects of chemotherapy in patients with advanced pancreatic cancer.

Purpose: Capecitabine-based adjuvant chemotherapy for colorectal cancer patients often causes adverse events (AEs), such as diarrhea, stomatitis, anorexia, and hand-foot syndrome (HFS). Cystine and theanine were reported to attenuate some chemotherapy-associated AEs, and hence are also expected to attenuate capecitabine-induced AEs. Therefore, we aimed to investigate the safety and efficacy of cystine/theanine treatment in colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery. Methods: A total of 100 colorectal cancer patients treated with capecitabine as an adjuvant chemotherapy after surgery were randomly allocated into the cystine/theanine group (n = 52) or the placebo group (n = 48). The primary endpoint was incidence rate of diarrhea of grade 1 or higher in accordance with the Common Terminology Criteria for AEs (CTCAE) v.4.0, Japanese Clinical Oncology Group (JCOG) version. The secondary endpoints included incidence rates of other AEs (CTCAE v.4.0-JCOG), as well as the incidence rate of HFS according to the HFS grading scale. Results: There were no significant differences in capecitabine-induced AEs between the two groups. However, the incidence rate of diarrhea of grade 1 or higher tended to be lower in the cystine/theanine group than the placebo group (18.4% vs. 28.9%, p = 0.169) as well as the incidence rate of HFS of grade 1 or higher (CTCAE v.4.0-JCOG or HFS grading scale) (67.4% vs. 77.8%, p = 0.185, 67.3% vs. 80.0%, p = 0.124, respectively). Conclusion: This trial demonstrated that cystine/theanine treatment of colorectal cancer patients undergoing capecitabine-based adjuvant chemotherapy after surgery is safe and has the tendency to reduce the incidence rate of diarrhea or HFS. Trial registration: UMIN000024784

Background: The acidic tumor microenvironment is associated with progression of cancers. The purpose of this study was to investigate the association between an alkaline diet and the effect of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) in non-small cell lung cancer (NSCLC) patients. Patients and Methods: Eleven advanced or recurrent NSCLC patients with EGFR mutations treated with EGFR-TKI after being instructed to follow an alkaline diet were retrospectively evaluated. Results: The median progression-free survival (PFS) and overall survival (OS) were 19.5 (range=3.1-33.8) and 28.5 (range=15.4-46.6) months. The average dosage of EGFR-TKI was 56±22% of the standard dosage. Urine pH was significantly increased after the alkaline diet (6.00±0.38 vs. 6.95±0.55; p<0.05). Conclusion: An alkaline diet may enhance the effect of EGFR-TKI treatment in NSCLC patients with EGFR mutations.