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Passed away: 9/12/09
Our journey started 4 years ago in June 2003. My son was operated twice at MSKCC in New York and treated with the usual two protocols consisting of Doxorubicin (Adriamycin), Vincristine, Cyclophosphamide and later Ifosfamide and Etoposide. Two years later the doctors “gave up”. They diagnosed that there was a recurrence with metastasis in many organs, refused to operate him again and only gave him Gleevec. First, we knew that my son was C-Kit negative and that Gleevec wouldn’t work for him; second, we knew that a single drug would NEVER work against DSRCT; third, other doctors in Brazil and US questioned their diagnostics of a spread disease.
We moved from MSKCC to Mount Sinai Hospital in New York. My son was then operated for the third time in the abdominal area. Later scans confirmed that the disease had not spread out of the abdominal area. My son was then for the second time on remission and we started an experimental treatment in Brazil advised by a preeminent US scientist consisting of anti-testosterone (Lupron + Casodex) plus Rapamycin plus Curcumin and no cytotoxic (chemo). Some enlarged nodules appeared in the lymph nodules of the pelvis on the 10th month but didn’t evolve so we thought it was only a sign of infection. Finally on the 14th month the scans showed a metastatic disease in many organs.
We went back to Mount Sinai for a 4th surgery extracting nodules form the right and left pelvis, liver and diaphragm. Three weeks later he was again operated (5th time) in Brazil of the left lobe. We strongly believe that a good debulking surgery is still the best single treatment for the disease.
I then met Dr. K. at the Pediatrics Dept. of MSKCC. He then recommend me a protocol he was successfully using against Neuroblastoma consisting of Temozolomide (Temodar) 150 mg/m2 per day oral one hour before Irinotecan (Camptosar) 50 mg/m2 per day IV for 60 min for 5 consecutive days. We opted to use it every 28 days and not 21 days and treat my son at home instead of as an outpatient in a hospital. We then returned to Brazil because we wanted to add some drugs to the cocktail that some doctors agreed in the US but wouldn’t be allowed to use because of its experimental character.
We thought my son was again on remission but to our surprise right after the first cycle of chemo the PET and CT scans showed an enlarged lymph node at the left pelvis and a thickening of the right hemithorax (where he was not operated).
We then restarted the Rapamycin (obs: AP23753 being tested by some patients is an analog to Rapamycin). We also added again Curcumin. The reasoning behind the use of those two drugs was because I brought from Japan (Dr. Jun Nishio) to the US three years ago the unique DSRCT cell line (live) available at that time and we tested in-vitro in the lab quite successfully against Rapamycin and Curcumin. You can search at Google Scholar or PubMed innumerous papers written about those two drugs. We knew they were quite active but we also had already learned that they were not sufficient to kill the disease.
Three months later the nodules and thickening disappeared from the scans and my son entered remission once again. My son used the above mentioned protocol for over 12 months and 14 cycles.
We learned that we cannot sit and relax while on remission. We must keep fighting it continuously otherwise it will most probably come back. The whole concept we are adopting advised by the above mentioned US scientist consists of activating the death pathways of the tumor cells with chemotherapy and simultaneously blocking the survival pathways of the tumor cells with other mechanisms (in other words trying to block the development of resistance to the chemotherapy).
For the last 5 months we added Sutent to the cocktail. It is one of the newest drugs available. It is a multi-kinase inhibitor and blocks many signaling pathways. It is also anti-angiogenic which means it blocks the development of new blood vessels to the tumors. No one had ever tried together with Temozolomide and Irinotecan. We opted for a Phase I trial at home. We started with ¼ of the recommend dose in the monotherapy trials and avoided using it during chemo days. Later we increased to ½ dose and later we started using it continuously at 1/2 dose.
The only important side effect my son has suffered was diarrhea. Irinotecan is known for late diarrhea but in the beginning he suffered more than most of the patients: ten days of diarrhea, mostly 24 hours a day, even using 2 tablets of Immodium every 2 hours, or Lomotil or any other drug available. He was hospitalized once for dehydration. I then searched all over the world and found a treatment being used by Dr. Takeda in Japan that consisted of alkalization and control of defecation. My son starts the treatment one day before chemo and uses it until the day after chemo. The treatment is a success. Nowadays he still has 6 days of late diarrhea concentrated right after the meals but he doesn’t use any drugs against it and consequently avoids drowsiness.
Contrarily to what we expected Rapamycin, Curcumin and Sutent didn’t aggravate the late diarrhea. They cause an eventual diarrhea after the “late diarrhea” period that can be easily controlled with a single pill of Immodium.
I exchanged information with the a few other patients of the Group who used Temozolomide + Irinotecan but it didn’t work for them. One explanation could be that the disease was already in a more advanced stage or that they didn’t use the additional drugs we added to the cocktail. I remind you that Dr. K., who has been helping us just as an adviser, has been using this protocol as a maintenance drug for remission.
Let me answer your questions and simultaneously tell you what I presently believe:
1. Surgery is the most effective treatment. If debulking is not possible, try at least to minimize the disease so chemo could work. Be very aggressive and fast with surgery.
2. The most successful cases seem not to have stopped doing something even after remission. If the body stands you have to keep the tumor continuously in check.
3. We never used radiation but looking back it seems to be a role for IMRT when the disease is first discovered and when the metastasis is still local.
4. DSRCT is chemo-sensitive to a wide variety of drugs. This is very good. That’s why Doxorubicin, Vincristine, Ifosfamide, Irinotecan plus a few others work. The problem is that like other types of tumors (1) the chemotherapy is toxic and cannot be used in the long-term; (2) there is a continuous risk of development of resistance; and (3) chemo works much better when the tumors are not large.
5. The difference of the Temozolomide + Irinotecan protocol is that it could be used in the long-term . I think it is the most importance part of the cocktail I gave to my son. It seems not to work that well when there is a large disease.
6. Rapamycin and Curcumin work because of (1) the present extensive worldwide research; (2) our in-vitro research with the Japanese DSRCT cell line; and (3) the fact that my son lived 10 months on remission using them without chemotherapy. They are not sufficient by themselves in the long-term. They work by controlling the development of resistance. You misunderstood my comment. I never used them together. Actually I never used two drugs without a minimum interval of 2 hours between them. Curcumin has to be stopped three days before chemotherapy because it is anti-oxidant and can be restarted the day after chemo. In the past I gave my son around 7 grams a day. Later I gave him around 2.5 to 3 grams a day because of the other drugs in the cocktail and the potential increase of the diarrhea. Buy the best Curcumin at www.lef.org. Curcumin's bioavailability is around 1% which means only 1% of what you get goes to the blood. The curcumin I recommended is added to Bioperine (a type of pepper) and has a 20 % biovailability according to tests.
7. Rapamycin (Rapamune) can be used continuously. The levels of Rapamycin in the blood could vary between 3 and 18 (www.questdiagnostics.com). In the past I tried to keep it around 13. Last time I aimed a lower lever (6 to 7) because of the other drugs in the cocktail, the potential increase of the diarrhea, and because there was an article about Kaposi sarcoma (which is very different from DSRCT) that showed that lower doses worked better than higher doses. It is impossible to translate blood levels into dosage because one patient may need only 1 mg a day to reach the level and other patient may need 4 mg a day.
8. Sutent is still a question mark. My son used it for 5 months. We already know that the dosage he used (25 mg per day) doesn’t seem to add toxicity. I used Sutent not because it is C-Kit inhibitor but because it is anti-VEGF and anti-PDGF, affecting angiogenesis and tumor stabilization and proliferation. I used it because the critical period which started six months after remission was getting closer and I thought we had to run a controlled risk in order to have stronger tools.
9. Overall I believe that what works is the cocktail as a whole since each piece has a different purpose. As long as the toxicity is low and controllable adding drugs that make sense could be the way for a long-term stabilization and control of the disease. I think it is still too early to use the word cure for any treatment or protocol.
I tried to correct the previous text to place it in the past tense since my son stopped chemo in September 2007. After that we decided for a consolidation which means giving a high dose chemo and subsequently a rescue of autologous stem cell transplant. His body was getting tired of the chemo for the first time and it took 5 weeks to recover from the 14th cycle. The protocol was a mobilization chemo consisting of Cyclophosphamide + Etoposide for three days followed two weeks later by stem cell collection at Westchester Medical Center, New York. When recovered he got the high dose chemo of Mitoxandrone + Carboplatin + Thiotepa for three days followed one week later by the autologous stem cell transplant. He remained hospitalized for 22 days. His neutrophils went to almost zero, the platelets to 12, but surprisingly he did not get any fever neither bleeding. We returned to Brazil in November 2007. He is not taking any drugs for the first time (against my previous recommendation). What happens is that his body needs time to recover from the chemo and the transplant. The first PET and MRI scans three months after transplant were negative. He will probably restart Curcumin and/or Rapamycin and/or Sutent and/or IGF-1R blocker (being tested by Roche) on the 6th month after the transplant. All four block one or a few survival pathways of the tumor cells and fight angiogenesis. My son recovered outstandingly well from the transplant, is feeling well and is in excellent mood. The only side effect which remains is intermitent diarrhea every three days controlled by Immodium.
- Surgery 1
- Surgery 2
- Surgery 3
- Surgery 4
- Surgery 5
- 6 sessions of Adriamycin (Doxorubicin);Cytoxan (Cyclophosphamide); Vincristine
- 6 sessions of Ifosfamide and Etoposide
- 14 months of anit-testosterone (Lupron+Casodex); Rapamycin; and Curcumin
- Dendritic vaccine
- Dendritic cells are the ones which contain/stimulate the killer cells which kill what goes wrong in our body, including tumor cells. When the dendritic cells either don’t identify or don’t send the message identifying a “stranger” in the body the tumor cells are allowed to grow.
- Irinotecan(Camptosar) and Temozolomide (Temodar)
- Rapamycin (Rapamune)
- High-dose chemo followed by autologous stem cell transplant
|8/03||0||Chemotherapy||Vincristine, Doxorubicin, Cyclophosphamide 1||0|
|9/03||0||Chemotherapy||Vincristine, Doxorubicin, Cyclophosphamide 2||0|
|10/03||0||Chemotherapy||Vincristine, Doxorubicin, Cyclophosphamide 3||0|
|11/03||0||Chemotherapy||Vincristine, Doxorubicin, Cyclophosphamide 4||0|
|12/03||0||Chemotherapy||Vincristine, Doxorubicin, Cyclophosphamide 5||0|
|1/04||0||Chemotherapy||Vincristine, Doxorubicin, Cyclophosphamide 6||0|
|3/04||0||Chemotherapy||Ifosfamide, Etoposide 1||0|
|4/04||0||Chemotherapy||Ifosfamide, Etoposide 2||0|
|5/04||0||Chemotherapy||Ifosfamide, Etoposide 3||0|
|6/04||0||Chemotherapy||Ifosfamide, Etoposide 4||0|
|7/04||0||Chemotherapy||Ifosfamide, Etoposide 5||0|
|8/04||0||Chemotherapy||Ifosfamide, Etoposide 6||0|
|6/05||0||0||Anti-testosterone; Rapamycin; Curcumin 1||0|
|7/05||0||0||Anti-testosterone; Rapamycin; Curcumin 2||0|
|8/05||0||0||Anti-testosterone; Rapamycin; Curcumin 3||0|
|9/05||0||0||Anti-testosterone; Rapamycin; Curcumin 4||0|
|10/05||0||0||Anti-testosterone; Rapamycin; Curcumin 5||0|
|11/05||0||0||Anti-testosterone; Rapamycin; Curcumin 6||0|
|12/05||0||0||Anti-testosterone; Rapamycin; Curcumin 7||0|
|1/06||0||0||Anti-testosterone; Rapamycin; Curcumin 8||0|
|2/06||0||0||Anti-testosterone; Rapamycin; Curcumin 9||0|
|3/06||0||0||Anti-testosterone; Rapamycin; Curcumin 10||0|
|4/06||0||0||Anti-testosterone; Rapamycin; Curcumin 11||0|
|5/06||0||0||Anti-testosterone; Rapamycin; Curcumin 12||0|
|6/06||0||0||Anti-testosterone; Rapamycin; Curcumin 13||0|
|7/06||0||Surgeries #4 and #5||0||0|
|8/06||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar;||0|
|9/06||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin||0|
|10/06||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin||0|
|11/06||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin||0|
|12/06||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin||0|
|1/07||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin||0|
|2/07||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin||0|
|3/07||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin||0|
|4/07||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin; Sutent||0|
|5/07||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin; Sutent||0|
|6/07||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin; Sutent||0|
|7/07||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin; Sutent||0|
|8/07||0||Maintenance Drugs / Chemotherapy||Irinotecan and Temodar; Rapamycin; Curcumin; Sutent||0|
|9/07||0||Mobilization Chemotherapy/Stem Cell Collection||Cyclophosphamide; Etoposide||0|
|10/07||0||High-dose Chemotherapy/Autologous Stem Cell Transplant||Mitoxandrone; Thiotepa; Carboplatin||0|