Category: Oncology

IV Curcumin with Paclitaxel: RDBPCT in Women with Stage III or IV Breast Cancer

This was a phase II trial comparing IV curcumin with paclitaxel to IV placebo with paclitaxel in women (N=150) with locally advanced or metastatic breast cancer. While participants could have tumors with any receptor status, the majority (57%) had HR+/Her2(-) disease. Patients received IV therapy once weekly for 12 consecutive weeks as follows:

-Premedication with dexamethasone 8mg
-Active intervention (Curcumin 300mg with pharmaceutical grade emulsifier) or placebo (riboflavin 200mg) dissolved in 250mL NaCl
-Paclitaxel 80mg/m2 in 250mL NaCl

There were no complete responses in either group. However, there were significantly more partial responses in the curcumin group compared to placebo (51% vs 33%; p=0.0145). Three months after completion of treatment, ORR remained higher in the curcumin group (45% for patients who completed treatment with curcumin, versus 28% for those who received placebo; p=0.03), suggesting that efficacy may be maintained even after terminating treatment.

There were no significant differences in adverse events, with the exception of fatigue, which occurred more often in the placebo group (p=0.05). Allergic reactions did not differ between groups. There were no deaths during the trial.

Citation:

Saghatelyan et al. Efficacy and safety of curcumin in combination with paclitaxel in patients with advanced, metastatic breast cancer: A comparative, randomized, double-blind, placebo-controlled clinical trial.  Phytomedicine. 2020 Apr 18;70:153218

Link:

https://www.sciencedirect.com/science/article/pii/S0944711320300507?via%3Dihub

Red clover extract for premenopausal women with breast cancer taking tamoxifen

In this prospective double-blind randomized placebo-controlled trial, 81 premenopausal women with non-metastatic ER+ breast cancer were given either a red clover extract at 80mg daily (n=42) or a placebo (n=39) for 24 months. All participants were receiving tamoxifen, and were also counseled on both physical activity and Mediterranean diet.

The red clover group had significantly greater improvements in waist circumference as well as BMI (p < 0.0001 for both). Aside from this, both groups experienced significant improvements in HDL (p = 0.01), menopausal symptoms (p < 0.0001), and breast density (p < 0.0001), suggesting that Mediterranean diet and exercise alone were responsible for these changes. Endometrial thickness did not change, and when serum from both groups was applied to ER+ breast cancer cells, there was no alteration in proliferation or estrogen-related gene expression.

It has been my practice to have women who are survivors of ER+ breast cancer avoid supplements containing phytoestrogenic herbs due to lack of safety data, so this (nonetheless small trial) is interesting to see.

Citation:

Ferraris et al. Red clover and lifestyle changes to contrast menopausal symptoms in premenopausal patients with hormone-sensitive breast cancer receiving tamoxifen. Breast Cancer Res Treat. 2020 Jan 24.

Link:

Red clover and lifestyle changes to contrast menopausal symptoms in premenopausal patients with hormone-sensitive breast cancer receiving tamoxifen

Phase I trial of intratumoral or intraperitoneal bromelain and NAC in patients with mucinous peritoneal tumors

In this Phase I trial, participants who had either declined surgery for, or were determined to be inoperable with, mucinous peritoneal tumors were administered a mixture of bromelain and NAC. Doses were based on estimated tumor volume as follows.

For people receiving intratumoral injection:

Bromelain 30mg and NAC 1500mg for tumor volume < 250mL

Bromelain 45mg and NAC 1500mg for tumor volume > 250mL or multiple treatment sites

For people receiving intraperitoneal injection:

Bromelain 45mg and NAC 1500mg for low tumor burden

Bromelain 60mg and NAC 2000mg for extensive tumor burden

A total of 20 patients underwent 28 treatments, with 13 receiving intratumoral treatment, and 7 receiving intraperitoneal treatment. The mean number of surgical procedures subjects had previously undergone was 3.8 (range 2-9). Primary tumor was appendiceal adenocarcinoma (N=10), mucinous ovarian tumor (N=3), colon cancer (N=1), or pseudomyxoma peritonei (N=6).

An objective response to Bromelain and NAC was seen in 30 of 41 treated sites (73.2%), in 85% of patients. Subjects received a mean of 4.2 doses. Adverse events occurred in 85% (N=17) of patients. There were a total of 88 adverse events, with 11 being serious treatment-related adverse events (12.5%). These included fever (35%) and grade II/III pain at drain site or during injection (30%).

This is the first trial of its kind examining such a protocol, with bromelain and NAC designed to essentially dissolve mucinous tumor masses, in humans.

Citation:

Valle et al. A novel treatment of bromelain and acetylcysteine (BromAc) in patients with peritoneal mucinous tumours: A phase I first in man study. European Journal of Surgical Oncology 2019 Oct 31. pii: S0748-7983(19)30913-8.

Link:

https://www.sciencedirect.com/science/article/pii/S0748798319309138 

NAC rinse reduces xerostomia in head & neck cancer patients receiving chemoradiation

This was a pilot scale double-blind, placebo-controlled randomized trial of a NAC rinse in people receiving chemoradiation for head and neck cancer. Patients were randomized to use either a 10% NAC rinse (100 mg/mL; 5 mL per rinse) or a sodium chloride placebo rinse in an FDA-approved diluent. Participants were advised to gargle with 5 mL of the solution for 60 seconds, and swish and spit 5 times daily both during radiation and for 2 weeks after completion of chemoradiation. For those in the treatment group, this provided a total NAC dose of 2500mg daily. Thirty-two participants were enrolled, with 17 receiving placebo, and 15 receiving NAC. The majority of subjects were receiving cisplatin.

NAC rinse was better than placebo for ameliorating thickened saliva and mucositis. The NAC group also had improved swallowing scores (p=0.17), and all scores for measures of pain, xerostomia, and trouble with social eating were better in subjects in the NAC group (all p values <0.20). There were no significant differences in adverse events between the NAC and placebo groups.

Citation:

Sio TT, Blanchard MJ, Novotny PJ, Patel SH, Rwigema JM, Pederson LD, McGee LA, Gamez ME, Seeger GR, Martenson JA, Grover Y, Neben Wittich MA, Garces YI, Foote RL, Miller RC, Halyard MY. N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2): A Double-Blind Randomized Clinical Trial. Mayo Clinic Proceedings. 2019 Aug 9. pii: S0025-6196(19)30396-9.

Link:

https://www.sciencedirect.com/science/article/pii/S0025619619303969