This is a short post to share with you a method for treating triple negative breast cancer, and potentially other cancers, involving:
- one or more checkpoint inhibitors in low dose
- hyperthermia treatment
- low dose chemotherapy
- lnterleukin-2 (IL-2)
- taurolidine [I discussed taurolidine in another post on this website (Ref.)]
As you probably know, at this point I still do not like the mainstream immunotheraphy due to its side effects and reduced effectiveness. This is why I am happy when I come across techniques that can reduce the side effects of imunotheraphies while increasing their effectiveness.
The patent shared with you here, suggests a treatment strategy that may achieve just that, i.e. improved effectiveness while using lower doses of conventional therapies.
Nevertheless, I still prefer the treatment strategies that are build around the metabolic perspective, as I feel that angle is both more effective and controllable as compared to treatment strategies build around the immuno perspective, such as the one discussed here.
Here you can read the patent: https://patents.google.com/patent/WO2017158570A1/en
The method patented here represents a typical treatment strategy that can be accessed at private clinics around the world. Often, German clinics are using low dose immunotherapy drugs in order to reduce the side effects. Sometimes, private clinics use even 6x or even 12x lower monthly dose compared to the one suggested by the drug supplier. Nivolomab as it was used here at 0.5 mg/kg each week, represents 2mg/kg/month, that is about 3x lower dose compared to the monthly recommended dose.
In their patent, the authors share one example of a triple negative cancer patient who benefited from such a treatment strategy. Here is the case report discussed in the patent:
“Example 2: Human Treatment Case Study
Patient Diagnosis and History before Study:
September of Year 1 : A fifty year old Caucasian female with histological diagnosis of triple negative breast cancer of the right breast 3 cm G3, CS axilla (histologically G3 with medullary shares, ER, PR and Her 2-new negative).
Disseminated lung metastasis.
Ki-67: 61% indicative of very high breast cancer cell division.
Additional evidence of ductal carcinoma in situ (DCIS) with focal vascular invasion; BRCA1 neg.
Before entering the study, the patient had been treated with numerous oncology and chemotherapy treatments including weekly neoadjuvant Taxol chemotherapy, lumpectomy with wide local excision, and adjuvant radiotherapy of the right chest wall. These treatments were ineffective and the patient developed metastatic dissemination and neutropenia, and was an end-stage (stage IV) patient.
Patient began the study having a Karnofsky score of 80%, mild neuropathy with distal emphasizes in all four extremities; and also suffered from severe pain during inspiration left lateral chest wall; for example, sneezing extremely painful, severe shortness of breath (SOS) on exertion, lack of appetite, insomnia, and exhaustion.
Diagnosis: Breast Cancer ICD10: C50.9
Lung Cancer ICD10: C78.6 Lymphadenopathy ICD10: R59.1
The patient underwent a four week Treatment Protocol as follows:
1.Weekly low-dose checkpoint inhibitor therapy with PD1/PDL-1 inhibition with nivolomab (0.5 mg/kg) and CTL-4 inhibition with ipilimumab (0.3 mg/kg) over three weeks.
2.Loco-regional hyperthermia with radiofrequency fields (13.56 MHz) using
Syncrotherm device 3 times per week over the thoracic region in combination with high dose vitamin C (0.5 g/kg) and alpha lipoic acid (600mg) over three weeks followed by:
1.Long duration (6-8 hours) fever range (about 42°C) whole body hyperthermia in combination low dose chemotherapy using cyclophosphamide 300 mg/m2 to down modulate TReg cells followed by:
2.Five days high-dose IL-2 (54 Mio I.U./m2 as decrescendo regime) therapy in combination with taurolidine (250 ml 2% Taurolidine, i.v.).
The inventors found that the combination of IL-2 and taurolidine was effective in inducing remission in the patient’s TNBC and metastases thereof, where the other treatments had failed.
The day after completing the multidisciplinary therapy, a chest x-ray demonstrated the far advanced bilateral pulmonary metastasis. The induction of a cytotoxic T-cell response following immunotherapy may take between 1 -2 months up to even 6 months. Thus, after 2 months the patient underwent a second chest x-ray which already demonstrated a 20% improvement in reduction of lung metastasis. A chest x- ray after a further 2 months demonstrated a remarkable partial remission. Further, the patient exhibited an excellent clinical condition with a Karnofsky score of 100% and absence of shortness of breath or any other cancer-related symptoms.
Both checkpoint inhibitor types (PD 1/PDL-1 and CTL-4 inhibition) were used to avoid autoimmunity following checkpoint inhibitor therapy. Specifically, nivolomab and ipilimumab were used in an off-label use in lower dosages and metronomically in higher (weekly) sequences.
Low-dose cyclophosphamide or gemcitabine therapy can selectively deplete T regulatory cells (Treg). Chemotherapy drugs (and irradiation) may be combined to break immune tolerance and create a tumor microenvironment for successful immune based therapies. Mild, fever range (40-42°C) prolonged whole body hyperthermia reduces interstitial pressure in the tumor microenvironment. Additionally, hyperthermia improves immunogenicity of cancer cells and lymphocyte trafficking. High-dose IL-2 has been known to have severe side effects and, as a result, IL-2 has never gained widespread use. The main side effects of high dose IL-2 therapy are induced by vascular leak syndrome with weight gain, generalized oedema, hypotension and impaired renal function being the main features. Vascular leak syndrome (VLS) is a life-threatening toxicity induced during IL-2 treatment of cancer patients. The co-administration of taurolidine, taurultam, oxathiazin-like compounds, and combinations thereof diminishes these vascular-leak induced side effects.
In summary, the present disclosure describes the demonstrated safety and effectiveness of the combination of IL-2 and taurolidine in inducing remission in the patient’s TNBC and metastases thereof, where the other treatments had failed.”
Reference: Method of treating triple negative breast cancer, 2016, https://patents.google.com/patent/WO2017158570A1/en
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