Is phase IV chemotherapy trial good to take ?

[anshul_15]

Hello!!!

I need a little bit of advice if anyone can suggest:

CASE HISTORY:

My mother who is 52 years old female, has recently been diagnosed for breast cancer.

She had been non diabetic, and a patient of hypothyroidism and (RA) rheumatoid arithritis. A brief history of hypothyroidism and Rheumatoid arithritis is as under:

Hypothyroidism: She has been suffering from hypothyroidism for about 12 years. Medicine taken: Thyronorm.

Rheumatoid Arithritis (RA): She has been suffering from Rheumatoid arithritis for about 18 years. Medicines taken: HCQS, SAAZ DS, Methotrexate, Arava, Medrol. A single dose of Rituximab injection was also taken in the year 2010.

Other details:

She is post menopausal since 10 years. She has 2 children. Her first child was born at the age of 25 years. She breast fed them for 3 months. She has never used oral contraceptives/ hormone replacement therapy. Both her mother and father were diagnosed for cancer but in their old age. Her mother had stomach cancer and father had prostate cancer.

Breast Cancer: (T2 N0 M0)

She was diagnosed with Right Breast Carcinoma (IDC) and underwent Right BCS with oncoplasty (J-Mammoplasty) + Sentinel Lymph Node Biopsy on 03-september-2015 under GA.

Tumor:

Infiltrating Duct Carcinoma (NOS), Grade III (MBR score 8/9)- Right breast

Foci of tumor cell necrosis are seen.

DCIS- Absent.

Lymphatic/Vascular emboli- Absent.

Stromal Desmoplasia- Absent.

Axillary Lymphnodes: Total – 3 nodes ALL FREE (0/3).

Sentinel- 0/2 (Both Free) ; Non sentinel – 0/1 (Free).

pTNM Stage: p T2 N0 (sn) (Carcinoma – Right BCS sample) - [T2 N0 M0].

IHC Result:

Estrogen receptor (ER) – Negative.

Progesterone receptor (PR) – Negative.

Her-2-neu (c-erb B2)= STRONGLY POSITIVE (Score 3+).

P53= Tumor cell p53 nuclear positivity – 35 to 40%.

Ki67= Tumor cell Ki67 proliferation index- 25 to 28 %.

Bone scan - negative.

After one week of surgery (BCS), she got infected with BILATERAL PYELONEPHRITIS along with SEPTICAEMIA (blood and urine culture positive for Ecoli, urine culture also positive for CRE (Klebsiella pneumonia) and remained hospitalized for about a month. Antibiotics administered during hospitalization were : Imipenem, Linezolid and Colistin. She is discharged and better now but still on oral antibiotics – Ferropenem and Nitrofurantoin. She is getting pus cells (about 10-15) in urine while still on antibiotics.

Now she has to undergo adjuvant chemotherapy along with radiation therapy.

There is a trial going ongoing for chemotherapy sponsored by Roche at MAX Parpargunj.

Details of trial:

Protocol Number: ML28714

Study Title: AN INDIAN MULTICENTRIC OPEN LABEL PROSPECTIVE PHASE IV STUDY TO EVALUATE SAFETY AND EFFICACY OF TRASTUZUMAB IN HER2 POSITIVE, NODE POSITIVE OR HIGH RISK NODE NEGATIVE BREAST CANCER AS A PART OF TREATMENT REGIMEN CONSISTING OF DOXORUBICIN, CYCLOPHOSPHAMIDE, WITH EITHER DOCETAXEL OR PACLITAXEL (AC -> TH) OR DOCETAXEL AND CARBOPLATIN (TCH).

My queries are:

1. Should my mother take the trial ? Is trial safer than normal chemotherapy?

2. If there would have been no trial, then do the prescribed medicines in the trial would still be the same as chemotherapy without trial ?

3. In the trial brochure given to patients, they have not mentioned anywhere about the dosage of medicines to be administered. So we are not aware of dosage of medicine to be given. So should we worry about the dosage of medicine in the trial?

4. Since there are so many chemotherapy regimes for breast cancer, which chemotherapy regimen would you have suggested (supposing there would have been no trial). Kindly also suggest the dosage of each medicine.

5. If you know, kindly tell us what kind of brand is ROCHE whose trial is going on?

Here I must include one more thing: Trial is free of cost to patients but that is NOT the reason we are considering to go for trial. My mother has enough health policies that she can easily go for normal chemotherapy (without trial). Money is NOT the consideration to go for trial.

We just want the right and safe chemotherapy treatment.

With enough hopes that you would help her take a better decision…. Thank you…..

[roxboxfox RadiationOncologist]

Dear Anshul,

You have very carefully drafted an excellent summary of your mothers history with her current cancer.

Its sad to see the problems she is currently been through especially the Bilateral Pyelonephritis.

I hope she is out of this episode completely, as if she has this relapse during chemotherapy it is very difficult to treat.

Your mother indeed is high risk in view of the Her2+ve, T2, Grade III histology

She certainly merits 3rd generation chemotherapy and Herceptin

I would certainly advise your mother to participate for the trial.

if she had refused the trial her options would be

3 # FEC ----> 3 # T

4# AC ---> 4 # T or 12 # Paclitaxel

6 # TCH

The dosages are pretty standard and if you are interested in the dosage ,

please refer to this link

clinicaltrials.gov/ct2/show...

In my practice, i advise chemotherapy with the least number of cycles which is 6

Many oncologists prefer 8 and 12

6 # TCH

3 # FEC ----> 3 # T

These are my favoured regimens, the chemotherapy is over within 15 weeks

as opposed to longer regimens which would take 21-24 weeks

(The former generate less income for doctors, the latter perhaps generate more income for doctors)

But legally, both these regimens are well tested and have equivalent efficacy.

I feel like giving my exams after a long time.....

The doses are std,

3 cycles of FEC -100 5FU 500mg/m2, Epirubicin 100 mg/m2, Cyclophosphamide 500 mg/m2 administered every 3 weeks.

All patients should have Ing Pegfilgrastim 6 mg sc on D2 or D3

as thisis highly myelosuppresive chemotherapy

Docetaxel 100 mg/m2 x 3 # administred every 3 weeks.

All patients should have Ing Pegfilgrastim 6 mg sc on D2 or D3

as this is highly myelosuppresive chemotherapy

the Trastuzumumab (Herceptin) is initiated with 4th cycle of chemotherapy with Docetaxel

loading dose 8 mg/kg, then maintenance at 6 mg / kg for total of 1 year

Roche is the pharmaceutical company;

They are the ones who have the original patent of this drug called HERCEPTIN

They have given this drug to Emcure, who brands this drug as Herclone

These are the only 2 companies who are legally allowed to sell their drugs

There is a high court order, withholding Herceptin for use by public ...by companies Biomab and mylan as Roche has sued these companies.

In this trial, you cannot decide what treatment you want, you will be randomly allocated AC-TH or TCH

Outside the trial your options would be 6 # TCH vs 3 # FEC --> 3 # Docetaxel

Of course Herceptin will follow from Day 1 with TCH, and with cycle 4 with FEC-T

Irrespective whether you go for the trial or not, it makes no difference

as she is on the right track... of chemotherapy + Herceptin

All the best

Dr Rohit Malde MD, DNB, FRCR (UK)

Consultant Clinical + Radiation Oncologist

Nanavati Hospital

Mumbai

[sumeet_shah Administrator in reply to roxboxfox]

Very beautifully explained, Rohit. Leaves me no room to add anything else

[anshul_15 in reply to roxboxfox]

Dear sir,

Thank you very much for your valuable suggestions.

So as you have suggested, the treatment regimens [ AC-->TH AND TCH] as mentioned in Trial are both correct for the treatment of my mother’s cancer. So I think we should go for the trial. Should we na ? just asking again as I was a little nervous.

If suppose we have to choose a better regimen out of two mentioned above, what shall it would be ?

Sir, it is a phase IV trial. What does that actually mean ?

Does medicines prescribed in the trial (including trastuzumab) approved by health authorities world wide to be used by patents.

Do doctors prescribe these medicines (including trastuzumab) OUTSIDE clinical trials ?

Sir, then what is the benefit of such a trial ?

Sir this trial is at MAX Parpargunj, Delhi under Dr. Meenu Walia. Delhi is very near to my hometown. I don’t know much about MAX medical oncology group and Dr. Walia. Sir,do you have any idea about MAX medical oncology division? because at the end everything depends upon the doctor who is treating the patient.

Sir, I was thinking to have a second report on the ER / PR / HER2 status of my mother’s cancer. Where can I send the slide and block for second opinion? Any well trusted diagnostic centre in INDIA or abroad is welcome.(Currently the ER/PR/HER2 status has been tested at MAX Labs only.) Should we also go for CEP17 gene test ?

Thank you in advance, sir...... your help would mean a lot for me in these circumstances of my family.

[manish_vkg TeamBCI in reply to anshul_15]

I dont have any idea about max oncology division but i know dr. Meenu Walia...she is wonderful doctor...she cares for paitients and treat them very well...answer all your query..salute to dr. Meenu Walia.

[roxboxfox RadiationOncologist]

Phase IV Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.

As of now, in terms of efficacy both regimens are the same.

In terms off toxicity, the TCH regimen has an edge, as it is an Anthracycline free regimen (mean less or no cardiotoxicity from Anthracyclines - Doxorubicin or Epirubin).

In the TCH regimen, your mother will have a total of 18 sessions of treatment ( 6 with chemo, and 12 without chemo) over a one year period.

The trial certainly is a good option.. But usually patients are encourage to enter trial for research purposes so as to help the future Breast cancer patients who will be treated in 2020 and 2025.

It was the brave women who have participated in trials conducted in 2000 and 2002, that today you have had the privilege of having TCH or AC--> TH

As i told you earlier, whether you participate for the trial or not, it does not matter as you are on the right track of having chemo + Herceptin.

You could repeat Her 2 testing, the current test you have done is on IHC,

If you go through one of your blogs on this site, we have discussed about Her2 status and our preference on getting this confirmed by FISH analysis, this is an expensive test costing upto 10K or so.

I would not have much information about the quality of testing in Delhi, perhaps a few members from this forum, can tell you about their experience.

RGCI, Apollo, etc all big name hospitals should be good enough, MAX should be good as well, only then would a big giant pharma company, have their product being used in an Indian Hospital in trial setting. They must have reviewed the hospitals machines and in house protocols.

It would be useful to get a second consultation from your local Oncologist, and trust him with his judgement as you are certainly on the right path.

The advise here should not be taken as substitute but we are here only to help, not to replace your oncologist.

Its always better to have second consultation, if you still have outstanding issues and queries as your right to know about the treatment from your oncologist

Best wishes

Dr Rohit Malde

[anshul_15 in reply to roxboxfox]

Thank you all especially Rohit sir for your wonderful advice.