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Regional chemotherapy (RCT) is chemotherapy restricted to one region of the body or to one organ. The principle of regional chemotherapy treatment is to reduce the size of typically extensive tumours without harming patients. Compared with systemic chemotherapy, RCT mitigates and largely prevents side effects by means of immediate post-treatment detoxification through chemofiltration. RCT can result in total tumour regression or a reduction in tumour size, including any regional metastases. It can also change a previously non-resectable (non-operable) tumor into a resectable one. Such remaining tumours can then often be removed surgically.
The choice of therapy procedure and the results of therapies depend upon a number of different factors. Some of the factors are, for example, the blood supply to the tumour and the effects of previous treatments (pre-treatment, including radiation therapy). Many other factors can affect the outcomes of the treatment, including the stage and the progression of the disease. Below is the therapy outcome-related data from some of the observations for several types of cancer. It is important to note that the majority of the data was collected based on the pool of patients with mostly advanced and metastatic stage-four cancers.

Mammary Carcinoma – Breast Cancer

Most effective method of RCT therapy is arterial infusion, which is administered through the artery that runs under the collarbone. This artery supplies the breast and the chest wall, as well as the lymphatic drainage regions on each side of the thorax. Treatment is performed in six cycles, with each cycle lasting five days and consisting of fifteen-minute arterial infusions with simultaneous blockage of the upper arm using an inflated blood pressure cuff. The treatment cycle is then repeated at four-week intervals. In case of a good response and a clear tumor regression following the initial therapy cycle, the patient has the option to consent to a surgical procedure to implant a permanent Jet-Port All-Round catheter. Such implant makes the treatment easier for both the patient and the medical team. Alternatively, the patient may continue treatment with an angiographically placed catheter. The arterial infusion procedure was performed for the first time in 1986 and has been considered standard ever since. Results:
  • Amputation can be avoided in most cases
  • Over 50% of the patients treated with arterial infusion show significant tumor shrinkage of over 50%
  • In 25% of cases the tumour complete disappears (clinically and histologically)
  • Side effects are significantly minimized. For example, hair loss is observed in less than 5% of patients
  • Drug streaming (a streaming phenomenon with skin and tissue irritation) in 4% of patients
  • Patients in good general performance have been able to work between treatments
  • Regional recurrence rate (T1 – T4: N0/N1) 17% during the interval between 9 and 16 years
 

Mammary Carcinoma – Thoracic Wall Recurrence and Lung Metastases

Thoracic wall recurrences often occur scattered along the anterior and lateral chest walls. Most of them tend to obtain all of their blood supply from a single artery. The Isolated Thoracic Perfusion (ITP) is used in order to simultaneously include all of the blood vessels that supply those tumours, in order to treat the recurrent breast cacner. Regional chemotherapy for the thorax in the form of Isolated Thoracic Perfusion with chemofiltration (ITP-F) is a very effective form of regional chemotherapy for primary and metastatic cancers affecting organs located in that area of the body. It allows to attain a very high level of cytostatic drug in the thoracic area. ITP-F also can help to deliver high concentrations of cytostatic drug to the organs in middle and lower areas of the body. High concentration of powerful cytostatic drugs could potentially lead to significant side effects in patients, unless it is combined with subsequent blood detoxification procedure. Using blood chemofiltration as a detoxification method, allows to minimize side effects and to improve patients’ tolerance to the treatment. Results:
  • For diffuse lung metastases in both lobes of the lung, the overall response rate is 71%.
  • Complete disappearance of the tumours in 26% of patients. This is identical to the results of regional chemotherapy for the primary mammary carcinoma.
  • Partial remission 45%
  • Survival rates:
    • 75% of patients survived for 13 months
    • 50% (median survival rate) survived for 20 months
    • 25% survived for 3 years
    • 10% survived for 10 years or more
  • For previously treated thoracic wall recurrences (especially after prior irradiation) the response rates are significantly less favourable than for patients who have not been treated previously.
  • Survival times in a total collective of 70 patients:
    • 75% survive for 9 months
    • 50% (median survival rate) survive 15 months
    • 25% survive 27 months
    • 10% survive 10 years or more
 

Advanced Ovarian Carcinoma

Therapeutic options for recurrent ovarian carcinoma are, unfortunately, limited. If there is a recurrence following combination chemotherapy with platinum-containing agents, life expectancy is poor. Until now, no other cytostatic drug combination has resulted in notable progress. Studies confirm that increasing the administered dosage of cytostatic agents greatly increases side effects, impairs quality of life and does not result in any prolongation of life. Regional chemotherapy for ovarian carcinoma has the goal of breaking through resistance to cytostatic agents by means of an increase in effective regional concentration of the drug. Subsequent chemofiltration of the blood serves to reduce the anticipated increase in toxicity immediately after the therapy and, therefore, makes the treatment tolerable. Results:
  • Complete disappearance of ascites (fluid in the abdomen) after only two isolated abdominal perfusion treatments in 45% of patients
  • Reduction of ascites by more than 50% in 18% of patients
  • Significant reduction in pain and abdominal symptoms in 74% of patients
  • Survival times:
    • 75% of patients survive for 7.5 months
    • 50% of patients (median survival rate) survive for 13 months
    • 25 % of patients survive 30 months
    • 9% survive recurrence-free for 5 years and longer (maximum 15 years)
  • Side effects remain within limits:
    • Bone marrow depression by WHO criteria II/II in one quarter (26%) of patients
    • Nausea occurred in 20%.
 

Pancreatic Carcinoma

Patients with pancreatic carcinoma generally have poor prognosis, since it is typically detected too late. Furthermore, it is located near anatomically important structures such as the bile ducts and major blood vessels, which complicates access to the tumor. At the time of diagnosis, only 10% of these tumours are still operable. For advanced pancreatic carcinoma, chemotherapy only prolongs life expectancy in the range of 2 to 6.5 months. Patients previously treated with radiation and chemotherapy are rarely included in the studies because of their poor prognosis. As a result, very few such studies exist. One study (Author: Berlin JD et al) reports a median survival time (50%) of 6.7 months in a large group of 322 previously treated patients, and a 25% survival period of 10.5 months. More recent studies of advanced, inoperable pancreatic carcinoma using newer agents could not demonstrate greater than 20-25% survival rate beyond one year. Regional chemotherapy for regionally advanced, inoperable and previously treated pancreatic carcinoma is performed using combined therapy, consisting of microembolization through angiographically placed catheters, followed by Isolated Abdominal Perfusion (IAP) to prevent or treat peritoneal (abdominal lining) metastases. Results:
  • 75% survive 6 months
  • 50% (median survival rate) survive 9 months
  • 30% survive 1 year and longer
  • 25% survive 18 months
 
Each patient’s tumor is different and has a unique pool of antigens (markers), which can trigger an immune response to the tumor. Many of these significant antigens are unique to that tumor only and are not shared among other tumors. These facts highlight the unmet need of personalized medicine. Vaccines are forms of personalized medicine, which can educate individual’s immune system to fight a particular cancer specific to this individual. Whole tumor personalized vaccine is a highly customized and personalized treatment derived from the patients’ own tumors. As noted above, such personalized medicine is designed to educate the immune system to fight one’s own cancer. Tumors have to be harvested in a sterile environment, usually at the time of a surgery. They are transferred to a specialized lab where tumor cells are manipulated to make them easier recognizable by the immune system. When that step is attained, it is expected that the immune system can mount a defensive attack against a specific cancer.
Not only does Regional Chemotherapy (RCT) allow to limit the side effects, which are associated with systemic chemotherapy, but also it induces a local killing effect on the targeted tumor. It releases all the tumor antigens into the blood system prompting the immune system to activate and act against the cancer tissue. However, such immune response only lasts for a limited time (usually a few days). The combination of RCT and personalized tumor vaccination can prompt patient's immune system to fight the cancer longer term. It can also be potentially effective in-parallel with other cancer treatments and regimens. Therefore, it can be beneficial as a part of multimodal cancer treatment approach.
Cancer or tumor immunotherapy can come in different forms nowadays. It could be drug based or cell based. Drug-based immunotherapies (with antibodies) are designed to activate the immune system without specificity. The whole tumor vaccination treatment is done in two stages. First, it is an induction of the immune system through RCT. Then, it is followed by personalized tumor vaccination in stage two. Personalized tumor vaccination is intended to trigger an immune response against patient’s own antigens, unlike drug-based immunotherpy. It is still experimental and much more personalized approach to cancer immunotherapy and cancer treatment in general.

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