Introduction

Ovarian cancer is the second most common gynecological cancer among American women, accounting for the most cancer-related deaths of the female reproductive system.¹ It is estimated that nearly 20,000 women in the United States will receive a new diagnosis of ovarian cancer in 2023. The overall rate of 5-year relative survival remains under 50%, with approximately half of all patients diagnosed being 63 years of age and older.²

The symptoms of ovarian cancer present vaguely, making diagnosis challenging. Traditional chemotherapy treatment for ovarian cancer consists of a platinum compound, either cisplatin or carboplatin, plus a taxane.

Paclitaxel (Taxol) is the most used medication of this class for this indication.^3,4 This drug course is administered every 3-4 weeks for 3-6 cycles of treatment, depending on the stage and type of ovarian cancer.^5,6

Unfortunately, patients with late-stage ovarian cancer develop chemotherapy resistance, worsening their prognosis. Recent studies have investigated the effects of curcumin (diferuloylmethane), a yellow polyphenol derived from turmeric (Curcuma longa L.), with the objective of enhancing the anticancer mechanisms of chemotherapeutics.^7,8

Diagnosis

After a pelvic examination, there are 2 methods utilized for ovarian cancer diagnosis, the first of which is a transvaginal ultrasound. This diagnostic technique remains an integral component of virtually every ovarian cancer screening algorithm, whether utilized for initial diagnosis or as a secondary test in patients having elevated biomarkers. An ultrasound wand is inserted into the vagina to generate ovarian images for detecting changes in organ morphology.⁹

The second diagnostic test performed is CA-125, the classical ovarian cancer biomarker.¹⁰ This antigen is not solely recommended in ovarian cancer screening.

This is because there are other conditions, such as endometriosis and pelvic inflammatory disease, that can present with high levels of this protein.¹¹ Although CA-125 is not sufficiently reliable in the diagnosis of early-stage ovarian cancer, it is a valuable indicator for evaluating chemotherapeutic efficacy and prognosis.¹²

Typically, in patients with high levels of CA-125 and a diagnosis of ovarian cancer, the protein level will decrease during treatment, which is a strong indicator that the patient is responding to the drug regimen. The US Preventive Services Task Force (USPSTF) recommends against screening for ovarian cancer in asymptomatic patients and those not known to have a high-risk hereditary cancer syndrome, such as Lynch Syndrome, a BRCA mutation, or family history of breast and ovarian cancer.¹³ Screening in low-risk individuals results in a high rate of false-positives, oftentimes resulting in unnecessary surgical procedures in patients not having cancer.¹³

Following a confirmed diagnosis, ovarian cancer is managed with a combination of surgery and chemotherapy, with surgery performed either before—called upfront or primary debulking surgery—or around the mid‐point of chemotherapy—called interval debulking surgery.¹⁴ The goal of this type of surgery is to remove as much of the visible (macroscopic) cancer tissue as possible, hence the name, debulking or cytoreduction.¹⁴

Drug Therapy

First-line chemotherapy for ovarian cancer is a platinum-containing agent plus a taxane. This regimen is administered either intravenously (IV) or through a combination of both IV and intraperitoneal (IP) route every 3 weeks for 6 cycles.¹⁵

Carboplatin is the preferred alkylating agent as it has a similar efficacy, with fewer renal and gastrointestinal effects than cisplatin.¹⁶ Paclitaxel is the most studied antimicrotubular and is used for ovarian cancer treatment. It has less myelosuppression than the other drug in its class, docetaxel.¹⁷ However, docetaxel is associated with a lower risk for neuropathy than paclitaxel and can be used as the alternative taxane drug.¹⁷

The antiangiogenic bevacizumab (Avastin) has been observed to act synergistically with carboplatin and paclitaxel. Therefore, it used for the management of stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following surgery (in combination with carboplatin and paclitaxel, followed by single-agent bevacizumab).

In 2018, bevacizumab received approval in the frontline, platinum-sensitive recurrent and platinum-resistant recurrent settings for the management of epithelial ovarian cancer.¹⁸ The adverse effects (AEs) of this vascular endothelial growth factor (VEGF) inhibitor include hypertension and proteinuria.

The poly (adenosine diphosphate–ribose) polymerase (PARP) inhibitor, olaparib (Lynparza) is approved for maintenance treatment in patients with platinum-sensitive relapsed ovarian cancer who had a response to their most recent platinum-based regimen, regardless of BRCA mutation status.19 In 2014, this inhibitor of DNA repair was approved for patients with advanced ovarian cancer and a deleterious or suspected deleterious germline BRCA mutation.

These patients were previously treated with 3 or more lines of chemotherapy, regardless of sensitivity to platinum-based therapy.¹⁹ Olaparib received an expanded indication in 2020. The drug can be used as maintenance therapy in combination with bevacizumab for first-line maintenance treatment of advanced ovarian cancer.²⁰

Curcumin combined therapy

Although chemotherapy remains the primary approved therapeutic approach in the treatment of ovarian cancer, it is limited by AEs, reduced response rate, and a high prevalence of relapse.²¹ Curcumin is a natural phenolic compound, used in Ayurveda and Chinese medicine.

This relative of turmeric possesses diverse therapeutic properties, such as anti-inflammatory, analgesic, antitumor, and antioxidant.²¹ For the management of ovarian cancer, it has been observed in both cellular and animal models that curcumin suppresses cell proliferation and promotes apoptosis.²²

Furthermore, curcumin when combined with chemotherapy is more likely to enhance the synergistic effect of cancer cells to drug therapy.²³ The addition of this phytochemical to current ovarian cancer chemotherapeutics may enhance drug cytotoxicity, while reversing multiple drug resistance, with nano-formulations of curcumin developed to increase the bioavailability of this natural product.²⁴ The administration of cisplatin and nanocurcumin in a rat model resulted in a significant reduction in ovarian tumor volume and weight, while downregulating signaling pathways, and reducing cellular viability.²⁴

A more recent study investigated the synergistic effects of curcumin and paclitaxel at reducing proliferation and promoting apoptosis in ovarian cancer cells.⁸ The cytotoxic effects of curcumin were reported to be a result of its regulation of miR-9 expression, with miR-9 known to regulate the gene expression of BRCA1.⁸

Recently, the first comparative clinical study was performed that evaluated curcumin’s effect in patients with breast cancer. Curcumin in combination with paclitaxel was superior to the paclitaxel-placebo combination after 12 weeks of treatment. In addition, IV-administered curcumin caused no major safety issues or reduced quality of life.²⁵

Prevention

Currently, there is no specific method for the prevention of ovarian cancer. Studies have observed that oral contraceptives used for 5 or more years, giving birth, or breast feeding for at least 1 year may reduce the risk.^26,27

Tubal ligation and a hysterectomy may provide some benefit.²⁸ Patients should discuss with their physician the most suitable option, with consideration to risks and benefits.

Conclusion

Ovarian cancer currently is the fifth leading cause of cancer-related deaths among women in the United States. The symptoms of this disease are vague and nonspecific, with no screening test presently available.

Treatment after final diagnosis is challenging, with surgery and chemotherapy remaining the main treatment options. As for the future of ovarian chemotherapy development, research continues to evaluate the most efficacious therapeutics, affording minimal toxicity to the patient.

Further studies are required to evaluate the use of curcumin as an adjunctive therapeutic option to currently approved chemotherapy.

References

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About the Authors

Rebecca Mathew and Christine Philipose are PharmD candidates (Class of 2024) in the College of Pharmacy and Health Sciences at St. John’s University, Queens, New York.

Maria A. Pino is an associate professor of Pharmacology at New York Institute of Technology College of Osteopathic Medicine (NYIT-COM) Old Westbury, New York, and Adjunct Assistant Professor in the College of Pharmacy and Health Sciences at St. John’s University, Queens, New York.