If standard cancer treatment fails, what’s next?

  • Alternative cancer treatment
  • Cancer treatment
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If standard cancer treatment fails, what’s next?

cancer treatment failsWhen standard cancer treatment fails, many patients and their families start anew, searching for alternatives. Cancer is one of the systemic diseases with the higher socioeconomic impact worldwide in terms of costs, loss of productivity and quality of life. Over the years, scientific advances have made it possible to successfully treat many types of cancer. Particularly progressed therapies for childhood cancers and dermatological malignancies.

Meanwhile, the treatment for solid tumors is still under intense research. Researches are taking into consideration directions to reach more cancer-selective approaches to treatments. Through this active search, novel therapeutic options become available. When standard cancer treatment fails or proves to be insufficient, many patients choose to look beyond standard protocols. But, how selection of cancer treatment happens? And, what options are there to choose from, when the first line treatment is not enough?

Selection of the standard cancer treatment depends on the clinicopathologic stage of the disease. Clinical signs and symptoms along with the results of the biopsies and imaging studies make up the TNM (tumor/node/metastases) schema. TNM is an internationally approved staging system that usually provides guidance for the selection of the most appropriate treatment strategy. Biochemical markers permit further stratification of cancer. Mutations testing such as ER, PR, KRAS and other help to evaluate responsiveness to treatment and prognosis of the disease. Surgical resection and postoperative systemic treatment are common strategies, but cancers in more advanced stages often do not respond to this approach.


Standard Cancer Treatments vs. Alternatives

Many years of trials have brought clinicians the understanding of a standard chemotherapeutic regimen for each type of tumor. For instance, leucovorin and irinotecan are often chosen for colon cancer treatment, and carboplatin and anthracyclines for breast cancer treatment. Unfortunately, in some cases standard regimens of cancer treatment fail. In those cases cytotoxic drugs in combination with molecularly targeted anticancer agents can offer an alternative. These are novel treatments that target biological processes and signal transduction pathways essential for tumor and metastasis growth.

Molecularly targeted agents can be chosen specifically according to the type of malignancy. For example, the anti-EGFR monoclonal antibody Cetuximab have been an option for colorectal cancer, while Trastuzumab for breast cancer. Still others have antiangiogenesis potential, making them a good choice to treat metastatic cancers. Combining treatments is the first option clinicians have when the standard approach does not work. However, alternatives in forms of experimental treatment strategies are available as well. Regional chemotherapy (or RCT) is one of them.


Regional Chemotherapy as Experimental Cancer Treatment

RCT is not a new treatment protocol. However, in some applications it is an experimental treatment, and very few medical teams can perform such therapies.

The simplest way of giving a chemotherapy dose is intravenously, through a slow infusion or a bolus injection (systemic chemotherapy). After administration, the distribution by the bloodstream allows the concentration of the drug to be almost the same in all parts of the body, affecting cancer cells wherever they are. For this reason, systemic chemotherapy is often used when there is suspicion or significant risk of having widespread cancer cells away from the primary tumor site. Unfortunately, such application permits the cytostatic drags to also reach and affect healthy organs. However, another option is regional chemotherapy, which targets cancerous tumors in a particular body region via arteries that are feeding the tumor regions. In this case, injecting the drugs directly into the artery can be more effective than systemic chemotherapy. Furthermore, specialized RCT protocols allow to keep the drugs away from the healthy organs, minimizing side effects.

Regional chemotherapy includes 4 different modalities: intraarterial infusion, isolated perfusion, chemoembolization, and top flow infusion. All of those modalities have the advantage of increasing tumor exposure to the drug at a much higher concentration rate. This capacity of regional chemotherapy often allows to break through drug resistance and is important for treating many types of tumors, including head and neck cancers, lung cancers, ovarian cancer and many other.

Regional chemotherapy can also be combined with systemic treatment in advanced cases where tumors do not respond to standard treatment options. In some cases, a combination of radiotherapy, regional chemotherapy, and surgery can provide better results than one modality alone. For this reason, when the outcomes of the chosen treatment options are not successful, oncologists should consider multimodal treatment approaches along with a multidisciplinary team expertise.


Combining Radiation and Chemotherapy

Radiation is the standard treatment for many cases of metastases to bone, brain, and other organs. Radiation can be used alone or in combination with systemic or regional chemotherapy, as well as other cancer therapies. The treatment depends on cancer cells’ sensitivity to X-rays or gamma rays. In some cases, it allows to avoid surgical involvement.

Combined treatment programs often employ radiotherapy. In some special cases it takes form of brachytherapy. Brachytherapy is a modality of radiotherapy, and it can be administered in two ways. One, high-dose radiation or HDR, is when special needles are inserted into the tumor to directly irradiate the cancer cells. Another is low-dose radioactive “seeds” that implanted into a tumor to provide a constant dose of low-energy radiation. Traditional radiation covers more easily the critical areas that need treatment, but brachytherapy delivers irradiation more specifically into the cancer tumor. The combination of both types of therapy can be equivalent to radical surgery in some cases, and it is a form of treatment for prostate cancers.

However, radiotherapy can damage surrounding tissues, as well as cause tissue fibrosis, which minimizes blood access to the tumor. If this occurs, the effects of chemotherapy on the tumor will be significantly impaired, as it is delivered via bloodstream. In such cases, if radiotherapy cancer treatment fails, the choices for the patient become narrow.


New Cancer Treatments and Multimodal Treatment Options

Finally, ongoing research prompts discovery of new treatment options, and some of them have had positive results, as in the case of monoclonal antibody drugs. These type of treatment employs antibodies with specific activity against certain cancers, such as Mabthera for lymphoma, Herceptin for breast cancer, and Erbitux in the case of bowel cancer. Herceptin, for instance, targets the human epithelial growth factor, which is higher in cancer cells.

Still other treatments under study are regional chemotherapy, heat therapy, cryosurgery, laser surgery, photodynamic therapy and gene therapy. Oncologists and scientists report promising results in many experimental treatment procedures. Some of them can make a difference, when the standard approach alone is not providing positive results. However, usually these treatment options can work in combination with chemotherapy, and only in some cases can substitute standard treatment.

Advanced and aggressive cancers can be unresponsive to one modality of treatment, and some cancer cells become resistant to systemic chemotherapy treatment and other drugs. Chemoresistance in cancerous is still a cause of an ongoing debate. Regional chemotherapy often allows to break through chemoresistance of a tumor, caused by systemic chemotherapy. It does it by delivering a powerful concentration of the drugs directly to the tumor site. Something that systemic chemotherapy cannot attain.

In conclusion it is important to note that, when standard treatments are not working, it becomes increasingly important to look for an out-of-the-box approach. One of such approaches is to work in cooperative multidisciplinary teams to devise and deliver the most effective multimodal treatment regimens to cancer patients.

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