SEF Chemo Patient Safety and Response Data

Updated May 21, 2017

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MEDICOR SEF CHEMO PATIENT RESPONSE DATA

We are currently in the process of computerizing our SEF chemo patient data collection. Once this is completed, we will be able to generate response data for all of the SEF chemo patients treated at Medicor, and we will be able to easily update the data on a regular basis. However, we manually collected data for the first 17 patients treated. This was at the start of the SEF chemo program in Toronto when the therapy was new to us. With any new treatment there is a learning curve, and we have improved upon this initial data.

 

DATA FROM CONSECUTIVE INITIAL SEF CHEMO PATIENTS, 2013 – 2014

Age Cancer Type Stage Prev Chemo? Reason Stopped Cycles Response Grade 3 or 4 Side Effects?
50 Lung (non-small cell) 4 Y DVT, pericardial effusion 5 Partial response (rapid visible improvement on chest x-ray) DVT/PE (after hospitalization & immobility)
62 Lung (non-small cell) 4 N Patient request 19 Partial response (clinical, CTC from 14250 to 0, PET/CT) No
61 Lung (small cell) 4 Y Cost 9 Partial response (CTC reduction, no visible tumours) No
52 Lung (non-small cell) 4 Y Low cell counts, progression 8 Partial response (rapid breathing improvement, ultrasound) PLT=15
53 Breast 4 Y Progression 7 Progression (imaging, clinical) No
63 Pancreatic 4 Y Fever / Infection 6 Partial response (Doppler – 4 of 5 liver mets dead after 4 cycles) Serosal mets & bowel perf likely due to rapid chemo action, occipital CVA in hosp after RBC transfusion
53 Pancreatic 4 N Cachexia 6 Partial Response pre: 6.4 x 3.4 x 4cm by CT, post 3.1 x 3.6cm by US
Weight loss, vomiting (iv Haldol & fluids in office)
46 Cervical 4 Y Completed 15 Complete Response (imaging, blood markers, CTC) ANC=0.3 after therapy completion, vomiting requiring iv fluids in office
69 Colon 4 Y Low cell counts 6 Progression (imaging, clinical) PLT=41
59 Gastric 4 Y (MTX for RA) Progression 10 Partial Response (loss of vascularity and decr size on ultrasound) ANC=0.8, PLT=38
41 Sarcoma 3 Y Progression 7 Progression (imaging, clinical) No
63 Bladder & Pancreas (neuroendocrine) 4 Y Low cell counts 10 Partial Response (pancreatic mass decr from 2.7cm to 1.2cm on CT) ANC=0.7
23 Melanoma 4 N Carbo Allergy 12 Partial Response (CTC reduction) PLT=44, vomiting (iv Haldol / fluids in office)
43 Colon 4 Y Jaundice 4 Not evaluable No
58 Liposarcoma 4 Y Low counts 11 Partial Response (CTC 4250 to 500) No
67 Prostate 4 N Completed 37 Partial Response (PSA 0.61 to 0.2, decr CTC) No
65 Breast 3 Y Decr Response 24 Partial Response (visual – skin mets only) Nausea / vomiting

ANC = absolute neutrophil count
CT = computerized tomography
CTC = circulating tumour cell count (# of cancer cells floating in the bloodstream)
CVA = stroke (cerebrovascular accident)
DVT/PE = deep venous thrombosis / pulmonary embolism
MTX = methotrexate
PLT = platelets
RA = rheumatoid arthritis
RBC = red blood cell
US = ultrasound

PR – Partial Response = 12 / 16 (75%)
CR – Complete Response = 1 / 16 (6%)
NR – No Response = 3 / 16 (19%)
Total Response Rate (PR+CR) = 81%

 

UNDERSTANDING THE DATA

To put this data into perspective, it may be compared against published phase 1 trial data of plain carboplatin administration without the protection of mesna. We have collected observational data of actual patients, outside of a clinical trial. However, since the data is from consecutive patients, in our opinion it can be reasonably compared against an open label phase 1 trial.

Comparison limitations:
1. One of the limitations in comparing the data is that patients were permitted to take concurrent natural medicines. Natural medicines could potentially enhance outcomes, but could just as easily interfere with SEF chemo and produce worse outcomes.
2. Another confounding factor is that patients are not accepted into a clinical trial if they don’t fit into specific parameters (e.g. certain blood tests must be normal or close to normal). We accept patients outside of such limits on a compassionate basis, so our patients may actually be more ill than those entering a trial. Accepting sicker patients tends to bias results against SEF chemo, making any favourable outcomes even more meaningful.
3. Another difference between the trial and our data is the chemo infusion speed. In the trial, carboplatin was given as a 24 hr infusion, whereas we administer it as a 30 minute infusion. It is possible the long infusion time caused greater toxicity.

When carboplatin was first used in humans, the dosing was calculated in mg per m2 of body surface area. Now dosing is calculated by the area under the carboplatin blood concentration/time curve (AUC). In the phase 1 trial a dose of 320mg/m2 given every 4 weeks was found to have dose-limiting toxicity. For our patients listed above, standard dosing was AUC4 – AUC5 every 2 weeks. Dose reduction to AUC3 was occasionally required. This corresponds to similar dosing as the clinical trial, with many of our patients actually receiving more chemo than the trial dosing of 320mg/m2 every 4 weeks.

In the clinical trial only 5 of 14 (35%) of patients treated were able to tolerate multiple cycles, with a mean number of cycles being just 5.2. In our data, all the patients were able to tolerate multiple cycles and the mean number of cycles was 11.5 (corrected for 1 patient who received 37 cycles that included 7 low dose cycles). Thus with the addition of mesna we were able to administer, on average, more than double the number of chemo cycles.

The main dose-limiting toxicity of carboplatin is a lowering of the platelet count. In the phase 1 trial, the rate of severe thrombocytopenia (platelet count < 20,000) was 6 out of 14 patients, or 43%. With our SEF chemo patients, the rate of severe thrombocytopenia was 1 out of 17 patients, or 6%. Thus carboplatin + mesna resulted in one seventh the number of cases of severe thrombocytopenia of carboplatin alone, despite (on average) double the number of chemo cycles being administered.

Carboplatin is a “broad spectrum” chemotherapy drug that works on many different cancer types. In the phase 1 trial, carboplatin was used to treat a variety of cancer types. In our data, a variety of cancer types were also treated, including some which typically do not respond well to chemo (e.g. melanoma or sarcoma). In the trial, response to therapy was seen in only 5 of 34 patients (15%). In our patients, responses were seen in 13 of 16 patients (81%). Our data shows a 5 fold improvement in response over the clinical trial of plain carboplatin. Although this is a reasonable comparison, it should be noted that some of our patients had responses measured by circulating tumour cell counts, whereas the trial only looked at visible tumour reduction. The reason we often utilize CTC counts to confirm response is that immunotherapies like SEF chemo frequently cause “pseudoprogression” on imaging (increase in tumour size which does not represent cancer growth). CTC counts help us determine the true response despite the limitations of scans when assessing immunotherapies.


MEDICOR SEF CHEMO SAFETY DATA

At Medicor, we have administered over 600 cycles of SEF chemo as of April 2017. Standard SEF carboplatin dosing is AUC4 every 2 weeks. This is more chemo than the typical dosing given in a hospital setting. For example for ovarian cancer, typical carboplatin dosing is AUC5 every 3 weeks (equivalent to AUC3.3 every 2 weeks). Patient data has been carefully recorded. Our findings are extremely favourable, confirming the high safety level of this therapy. Out of 600 cycles, the following rates of serious complications attributed directly to the therapy have been noted:

MI (heart attack): 0%

CVA (stroke): 0.16%

DVT / PE (life-threatening blood clot): 0.3%

febrile neutropenia (fever with low white cell count, requiring hospital admission for intravenous antibiotics): 0%*

tumour lysis syndrome: 0% (we have only treated a small # of cases of lymphoma and leukemia)

vomiting requiring hospital admission: 0.5%**

carboplatin allergy (life-threatening): 0.16%

carboplatin allergy (non life-threatening): 0.16%

death: 0%

*includes treatment of patients with active infections such as abscess, pneumonia and rectovesical fistula, which is not possible with regular chemotherapy

**not a chemo drug side effect, but caused by bowel blockage due to tumour inflammation after chemo, where there was an existing tumour pressing on the bowel
WITH routine use of ondansetron for all patients (some stop it on their own with no complications)
NO routine use of steroid, like dexamethasone (only for a small number of patients where there is tumour swelling causing bowel blockage or pressure in the brain)
NO routine use of aprepitant (only for a small number of patients who have a sensitive stomach)