Introduction

Cancer is a life-threatening condition that can be treated with the right approach. However, cancer treatment and management are challenging despite today’s medical advances. That’s why new discoveries in cancer therapies play a crucial role. One example is metronomic chemotherapy. 

Metronomic Chemotherapy (MC) is a relatively new approach to treating cancer that involves administering low doses of chemotherapy drugs over an extended period. It has been investigated in treating advanced Prostate Cancer (PC) for over three decades.

However, it is not considered a standard option for the early stages of metastatic castration-resistant prostate cancer (mCRPC) when highly active and well-tolerated novel hormonal agents are freely available. 

In this blog, we will explore the use of MC in treating advanced prostate cancer (PC). We will also discuss its benefits and the best MC combination for a subsequent phase II study.

What is the Definition of Metronomic Chemotherapy?

Metronomic chemotherapy is an anticancer treatment that involves the administration of anticancer medications in low and continuous doses. The duration depends on the severity of the condition and how the person responds to the drug. 

What’s more, metronomic chemo has fewer side effects compared to standard chemotherapy. Low doses of anticancer medications help prevent the growth of new blood vessels that tumors need to grow, develop and increase. Metronomic chemotherapy is also known as low-dose chemotherapy.

Mechanism of Action

Metronomic chemotherapy is a multi-targeted therapy. This means that metronomic therapy exerts direct and indirect effects on tumor cells within their microenvironment. MC inhibits the growth of new blood cells (angiogenesis), tumor growth, and metastasis. This treatment protocol shows potential in restoring antitumor immune response and induction of tumor dormancy.

Key Points

• The MC treatment protocol is based on the low administration of chemotherapeutic agents that typically results in minimal toxicity levels and no extended drug-free breaks.

• MC works well with anticancer therapies like conventional chemotherapy, targeted therapy, or radiotherapy.

• Initially, the original use of MC was to overcome drug resistance by changing the therapeutic target from tumor cells to tumor vasculature.

Understanding Metronomic Chemotherapy

Over the past three decades, medical experts evaluated various combinations of metronomic chemotherapy. However, most studies took place before introducing novel hormonal or cytotoxic agents. Moreover, most trials were small, non-randomized, or retrospective analyses.

Therefore, it is challenging to determine MC’s benefits. OMC showed potential as a therapeutic option for patients who were heavily pretreated with mCRPC. These patients failed the other available therapy options or were unfit for standard chemotherapy. 

Antitumor Activities of Metronomic Chemotherapy

Several studies demonstrated MC’s antitumor activities in advanced mCRPC patients. This was before the advent of novel, active therapies dedicated to this population. Metronomic chemotherapy showed positive results, especially in the elderly and frail patients representing most mCRPC patients. Therefore, medical experts concluded that MC has a very favorable safety profile. It is an ideal advanced prostate cancer treatment.

Studies involving the combination of MC and steroids further complicate MC’s validation of regular MC in mCRPC patients. Switching prednisone to dexamethasone in mCRPC patients treated with an abiraterone + prednisone combination led to profound biochemical responses. The simple switch underscores the risk of overestimating the benefit of MC, especially with patients receiving simultaneous dexamethasone treatment. 

Clinical Study

This section highlights the antitumor activities of MC in mCRPC patients pretreated with (docetaxel and ≥1 novel endocrine agent. Single-agent cyclophosphamide led to considerably low rates of Prostate-Specific Antigen responses of approximately 16%. Moreover, the PSF and Overall Survival (OS) of 4 and 8.1 months. Therefore, this clinical study demonstrated MC’s promising anticancer activities before the era of novel therapies. However, the results may not be easily reproduced in contemporary and standard mCRPC pretreated patients.

Benefits of Metronomic Chemotherapy

Medical experts analyzed cancer patients treated with various MC approaches to determine the optimal MC combination for a subsequent phase II study. No mCRPC patients were allowed to take corticosteroids during the treatment. However, pharmacological castration with LHRH analogs was continued.

The analysis included nine heavily pretreated patients, and most patients were initially diagnosed with aggressive PC (median Gleason score of 9). Patients received combinations of cyclophosphamide, vinorelbine, cisplatin, paclitaxel, and capecitabine. All patients tolerated the regimens well. Only the G1–2 myelotoxicity produced an adverse reaction. The biochemical responses in patients: ≥50% decline in PSA – 0%, 50%, 100%, and 100%. 

Based on the analysis above, medical experts chose the combination of paclitaxel + capecitabine + cyclophosphamide for further evaluation in a planned phase II clinical trial.  

Metronomic chemotherapy is a unique treatment option for advanced cancer patients, including those with metastatic castration-resistant prostate cancer (mCRPC). It is an effective option for later lines of therapy when no standard treatments or dedicated clinical trials are available. 

In addition, MC is ideal for fragile, elderly patients who may not tolerate standard treatment options and for low- and middle-income patients who do not have access to newer, more expensive anticancer agents. Although MC shows potential in cancer treatment, doctors should carefully consider using it in place of established treatments like enzalutamide, docetaxel, cabazitaxel, or abiraterone.

Recent studies show that checkpoint inhibitors with immunomodulating metronomic chemotherapy regimens may offer promising results in mCRPC patients. 

Conclusion

Metronomic chemotherapy is an effective treatment option for advanced cancer patients, especially when no other treatments are available or standard therapies are not suitable. However, the established or standard regimens should still be considered first. 

The future of metronomic chemotherapy lies in the data gathered by researchers about the best agents to use according to the type of tumor. This will help oncologists determine the proper dosing to treat certain cancer types. With data from additional research, doctors can choose the best usage for MC, whether as a single treatment or combined with other methods. 

Get the Right Treatment for Cancer and Live A Longer and Happier Life

There’s no denying that cancer is challenging to live with. It can affect your quality of life if left untreated. That is why the Institute of Integrative BioOncology is here for you. 

We specialize in cancer treatment and management. Our oncologists use innovative and conventional methods to provide the right treatment for you. Dr. Zhang has helped many patients achieve a happier and healthier life using efficient and proven cancer therapies. He has over ten years of treating gastroenterological, lung, and prostate cancers with a high success rate.

If you want safe and efficient cancer management, contact Dr. Paul Zhang, MD, at Omega Precision Oncology, a center for evidence-based cancer treatment.

You can reach him by dialing 7137971900.