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Read this today: Radiation 'Sandwiched' Twixt Chemo Cycles Combats Endometrial Cancer (UPSC particularly)

lindaprocopio's picture
lindaprocopio
Posts: 2022
Joined: Oct 2008

Someone else may have already posted this, & a lot of it is verification of the Yale study from long ago, but it just hit OncologySTAT this week:

Radiation 'Sandwiched' Twixt Chemo Cycles Combats Endometrial Cancer
Elsevier Global Medical News. 2011 Mar 14, D McNamara

ORLANDO (EGMN) - Adjuvant radiation therapy that was "sandwiched" between chemotherapy cycles of paclitaxel and carboplatin is "highly efficacious" in women with completely resected uterine papillary serous carcinoma, investigators reported, based on results of a prospective, phase II study.

"We noted a particularly high survival rate more than 50% at 3 years in stage III and IV patients who had no visible disease after surgery," Dr. Mark H. Einstein said at the annual meeting of the Society of Gynecologic Oncologists.

A total of 78 evaluable patients with histologically confirmed uterine papillary serous carcinoma (UPSC) began a regimen of three cycles of paclitaxel and carboplatin, followed by adjuvant pelvic radiation therapy, and then a subsequent three cycles of the same chemotherapy. Most women (82%) had stage I or II cancer (confined to the uterus), and the remaining 18% had stage III or IV disease.

Of the 78 women who started treatment, 72 completed the first three cycles and had some radiation, 67 completed prescribed radiation therapy, and 65 completed the full prescribed regimen, Dr. Einstein said.

Survival analysis was performed on the group of 72 patients. Median overall progression-free survival was 65.5 months for stage I and II disease, Dr. Einstein said. The overall progression-free survival for advanced disease with no gross evidence of disease after surgery was 25.8 months.

Median overall survival was 76.5 months for stage I and II patients and 35.9 months for the advanced stage patients. A calculated 3-year survival probability was 84% for women with stage I and II cancer and 50% for those with stage III and IV disease.

All study participants were treated during 1999-2010 at Albert Einstein College of Medicine/Montefiore Medical Center in the Bronx, N.Y., where Dr. Einstein is a gynecologic oncologist.

Enrollment took longer than 10 years, during which time there were changes in radiation therapy - a potential study limitation, said invited discussant Dr. Paola Alvarez Gehrig.
Nonetheless, this study is important, Dr. Gehrig said, because evidence-based guidelines for UPSC are limited. Also, a search for effective treatment is laudable because UPSC "is a rare but aggressive subtype of endometrial cancer." Although it represents 10% of endometrial cancer cases, UPSC accounts for up to 40% of endometrial cancer deaths (Brit. J. Cancer. 2006;13:642-6), the University of North Carolina at Chapel Hill.

The regimen consisted of paclitaxel at 175 mg/m2 and cisplatin (AUC [area under the curve] = 6) every 21 days for three cycles. Radiation treatment consisted of brachytherapy, external-beam radiation, or both, based on cancer stage and physician discretion. A total of 55 women had both therapies, 4 had brachytherapy alone, and 6 had external-beam radiation alone. The radiation field was extended for women with N2-positive pelvic disease or positive para-aortic nodes. The additional three cycles were paclitaxel at the same dose plus cisplatin (AUC = 5-6) every 21 days.

Median age was 68 years. Participants were 54% black, 41% white, 2.5% Asian, and 2.5% other. In terms of ethnicity, the cohort was 19% Hispanic and 81% non-Hispanic.

Based on these results, the researchers proposed that this "sandwiched" regimen be considered as an arm for future phase III clinical trials that assess patients with UPSC.

Toxicities were reported for the 78 patients who initiated therapy. Toxicity-associated dose delays and reductions primarily occurred after radiation therapy, Dr. Einstein said. "Only about 40% of these occurred before radiation therapy." Doses were reduced for 26 cycles (6.0% of 435 total chemotherapy cycles administered), and 37 cycles (8.5%) were delayed because of toxicities.

Grade 3 hematologic toxicities were noted in 62 cycles (14% of total) and grade 4 toxicities in 56 cycles (13%); neuropathy was the most common, followed by thrombocytopenia and anemia. Of the 16 grade 3 and 4 nonhematologic effects, infections (5), neuropathy (4), and deep vein thrombosis (3) were the most commonly reported. No participants died because of treatment.
The single-center study design is a potential limitation, Dr. Einstein said. In addition, although all women with stage III or IV had omental sampling, only 63% of early-stage women did, so some women may have been misclassified, he said.

The current findings build on a previous pilot study by Dr. Einstein and his colleagues. They demonstrated "excellent survival" among 30 women with no gross disease after initial staging surgery using a similar regimen (Gynecol. Oncol. 2008:108:201-6). "Based on the success of our pilot study, we expanded on the study with longer follow-up and toxicity assessment," Dr. Einstein said. Cisplatin dosing was lowered from the pilot study (initially up to 7.5 AUC) to reduce toxicity potential. "We've improved the protocols."

Other investigators have assessed various sequencing of chemotherapy and radiation. For example, in a study of 109 women with advanced endometrial cancer, 45 treated with chemotherapy followed by radiation and then more chemotherapy experienced improved survival compared with 46 who received chemotherapy and then radiation or the 18 who received radiation and then chemotherapy (Gynecol. Oncol. 2009;114:442-7).

Other researchers found "decent" progression-free survival and low recurrence rates, Dr. Einstein said, when 43 women with advanced endometrial cancer were treated with a regimen of four cycles of chemotherapy, then external-beam radiation, and then two more cycles of chemotherapy (Gynecol. Oncol. 2009;114:94-98).

Dr. Einstein and Dr. Gehrig said that they had no relevant disclosures.

firstsister
Posts: 13
Joined: Sep 2009

Thanks, Linda, for the article. I am undergoing this kind of treatment. I am 3-C and have had hysterectomy, three cycles of chemo (carbo/taxol) and completed 28 external beam radiation therapy. Going to start second three cycles of chemo in a week or so. So far so good. Have tolerated it all okay and my doctors seem pleased at how things are going. Thanks again for the info. Pat

RoseyR
Posts: 464
Joined: Feb 2011

Thanks for your comment and glad to hear you've had few effects from treatment so far.

Two questions:

Did you decide not to have additional brachytherapy after pelvic radiation or did your medical team think it wasn't warranted?

And have you had fairly bad diahrrea from the radiaiton?

Thanks,
Rosey

Kaleena's picture
Kaleena
Posts: 1226
Joined: Nov 2009

Rosey,

It is my understanding from my radiation oncologist that once you have brachytherapy, you can't have it again, or at least that is what they told me.

firstsister
Posts: 13
Joined: Sep 2009

Hi Rosey:

Brachytherapy has not been mentioned for me by either gyn/onc or radiation onc, just the pelvic.

I had some severe diahrrea with the radiation (I used imodium to good effect), loss of appetite and fatigue. I did pretty well for the first 4 weeks but the last two weeks were tough. Feeling much better now (a month since last radiation treatment), appetite coming back, energy levels up, diahrrea mostly gone - even ate some corned beef and cabbage for St. Patrick's Day with no ill effects.

Pat

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Ro10
Posts: 1482
Joined: Jan 2009

I also had 28 radiation therapy sessions in additional to being hospitalized for a 28 hour radium implant after the external radiation. I had not problems with diarrhea during my radiation treatments, and have not noticed any long term effects of the radiation. I finished my radiation in 5/09, and my last 3 chemos 8/09.

I am currently undergoing another round of Taxol/ Carbo for recurrence in my lymph nodes. I had 5/21 positive lymph nodes at diagnosis, along with metastic cells in the peritoneal fluid. I had minimal side effects from the first round of chemo.

Good luck to you Pat. Linda thanks for the information. In peace and caring.

minniejan
Posts: 88
Joined: Dec 2010

Good Morning,

Thank you for posting the study. The more information available the better! I have finished 3 brachytherapy and 2 chemo, carbo and taxol, and right now am wondering if I made the correct choice as I go through this. I am going through these two treatments concurrently for UPSC, Stage 1A. I will only have 3 chemo treatments and 3 brachytherapy treatments total. Anyone with UPSC Stage 1 A undergoing the same exact treatment?

MinnieJan

Rewriter's picture
Rewriter
Posts: 496
Joined: Dec 2009

Hi, MinnieJan--

I was diagnosed with Stage 1a mixed UPSC and endometriod adenocarcinoma in late April 2008, and my surgery was in May. The cancer was confined to a polyp and was completely removed during surgery. 29 lymph nodes, washings, biopsies of omentum were all negative.

My treatment, which ended in December 2008, comprised six rounds of carbo/taxol chemotherapy once every three weeks, followed by five rounds of once-a-week brachytherapy treatments. I was given the option of observation, as I assume was an option given to you as well. I preferred to follow the recommendation of my trusted gynecologic oncologist.

So far, so good. I assume that because my diagnosis was almost three years ago, the treatment recommendation given to me NOW might be the different. Did you get more than one opinion regarding your treatment protocol? Are you comfortable with your gyne-onc/medical oncologist and confident that they are up-to-date with the latest studies of UPSC? Those are the important questions.

If all of your cancer was removed at surgery, if you are truly Stage 1a (lots of lymph nodes tested, as well as pelvic washings, and omentum biopsies), and if you've had the treatment recommended by a trusted and up-to-date doctor, you should be just fine. May it always be so.

Jill

Pat51
Posts: 111
Joined: Feb 2011

I was recently diagnosed as a Stage 1 A/B. I was stage 1A on the new FIGO chart and stage 1B on the older system. I just had surgery a month ago, invasion on the inner 1/2 of the uterine wall and with a negative washing, 16 negative abdominal and arotic nodes, 6 negative peritneal biopsies, negative omentum, negative lympathic invasion. I was started on 6 chemo treatments on carbo/taxotere. I have had one chemo treatment and met with a radiation oncologist a couple of days ago. He is unsure of what, if any, radiation to do. He is leaning toward 3 brachtytherapy treatments but wants me to get second and third opinions. I guess that he does not see enough cases at my stage to feel confident with a recommendation. He said that all 6 chemo would be done before radiation.

Pat

willbesurvivor's picture
willbesurvivor
Posts: 50
Joined: Jan 2011

My mum's oncologist/surgeon who is apparently 'the best in the western world' said that the sandwich method is no longer the best method. Here is the link to his website http://www.obermair.info/ he has done a clinical trial on UPSC.

My mum is just getting 4 rounds of chemo, for stage 3C UPSC, which he also said is just as good as 6 rounds. Plus the pelvic radiation and brachy.

Hope this helps.

Tali

minniejan
Posts: 88
Joined: Dec 2010

Good Morning,

Thank you Pat and Jill. I did get two opinions, the other was wait and see, no therapy at all. I am as confident as I can be in the doctor I have at Penn. I actually chose him as he is supposed to be "top doc" in the Philly area for gyn cancer. And I felt confident he is in chief of gynecological oncology at teaching hospital and involved clinical trials. Only issue I have is that he is very confidently quiet and I have to ask all the questions. I am not shy about asking, and these studies have prompted me to list a new set of questions for him when I go in for my third chemo tomorrow.

I do have a copy of the surgical results, and it was confined to one polyp, all lymph nodes negative, negative omentum biopsies, no invasion of the uterine wall, etc.

MinnieJan

nancygt
Posts: 86
Joined: Jan 2010

I did have the exact protocol in first half of 09 as my initial treatment - 3 carboplatin/taxol followed by 6 weeks external radiation followed by 3 brachytherapy followed by 3 more carbo/taxol. This study is small, over 10 years old and a recent article I posted by three gyn/oncs at MD Anderson recommended brachytherpy only since surgery should have removed down to the cervical cuff which can be treated effectively with the brachytherapy. I have scarring in my colon, rectal bleeding, scarring in my ureters and this is one of the down sides of the external radiation. I recurred in my para-aortic lymph nodes only 5 months after the end of this maximum sandwich therapy -of course i was misdiagnosed a 3A when I really was a stage 4 USPC so perhaps the more rugged regimen is warranted for stage 1 or 2 but i would certainly get a second opinion.I am now on my second recurrence, taking Cisplatin and Adriamycin whcih are tough and I question is much of the urinary and bowel problems that are challenging me on this chemo come from overkill in the radiation area.

jmnye
Posts: 14
Joined: Feb 2010

I too, had the sandwich treatment for IIIc, but adenocarcinoma (sp?).

I had a 50% chance to make it 2 years.

I just had my 2 yr PET/CT and I am clean, clear, and healthy - no cancer!

Anyway, I just saw my doctor and I told her that she cured me! She said, "yes, I did!"

I am now on a 6 month check-up plan.

Ready for Spring,
Jane

firstsister
Posts: 13
Joined: Sep 2009

What wonderful news! Congratulations. Thanks so much for posting. What a boost for me.

Pat

RGK's picture
RGK
Posts: 20
Joined: Oct 2009

I had the sandwich method, too -- 3 rounds of carboplatin and taxotere, 26 external radiation + 1 brachytherapy, and 3 more rounds of chemo, for stage 3c endometrial adenocarcinoma. It was part of the Phase II clinical trial that I participated in, beginning July 2008. It made intuitive sense to me -- start with the systemic chemo, go for the local sites with radiation, and then follow with more systemic treatment. It was described to me as "aggressive," but appropriate for an aggressive cancer. I'm closing in on 3 years since my surgery.

laura25's picture
laura25
Posts: 160
Joined: Mar 2011

Hello... I am currently under treatment for endometrial adneocarcinoma and heard different reports on radiation. I will be finishing up my 3rd round of carbo/taxol and going for a PET scan. I am 45, thin and in great physcial condition (except for cancer).. did you have any long term side effects from the radiation treatment? I heard of vaginal shorting, bowel adhesion and bladder problems. I wonder if this is a "few" or the "norm"... thanks so much for any info you can provide.

Kaleena's picture
Kaleena
Posts: 1226
Joined: Nov 2009

Hello Laura:

Sorry you have to have found this site, but you will be glad you did. I was also 45 years old when I was diagnosed with endometrial adneocarcinoma. I started with the carbo/taxol but was allergic to taxol so they put me on carbo/gemzar. After that I had three brachytherapies. I did not have pelvic radiations because in my case the side effects outweighed the benefits because of all of my scarring. (I had three C-sections too). That was back in 2005. With brachytherapy you can get scarring. The long-term effects are basically unknown since each individual is different. But what can occur in the long run is scarring which may cause some blockages in the bowel and bladder as you have indicated. How soon or how long can you go without that is different for everyone.

With brachytherapy, they will give you a dialator which helps prevent scarring and shortining.

I hope this helps.

My best to you. I assume you are now halfway through your treatment.

Kathy

laura25's picture
laura25
Posts: 160
Joined: Mar 2011

Thank you Kathy for your response. It is sooooooo good to hear from some one who has walked the walk.
I just finished my 3rd treatment. My staging operation was quite long, my Dr took his time and removed anything that looked remotely suspicious. He wants me to do 8 treatments of carbo/taxol in all. He said I am young enough and in great shape that if my body can handle the 6 treatments then he would push for 8.
He didn't recommend radiation as of yet. This is so hard, I have a young child and can't picture the thought of leaving her behind. You gave me the best gift any one could give, hope.

Kaleena's picture
Kaleena
Posts: 1226
Joined: Nov 2009

Laura,

You are welcome. You seem like such a postive person. That is great. Positive thinking is one of the first defenses in fighting this stuff. With regard to radiation, at first they told me that I wouldn't need radiation, but they decided a year later that I would just have the 3 brachytherapies. I was upset at first because I wanted to be done with all of this. But realized it as just another "precaution".

When I was first diagnosed, my boys were 11, 13 and 15. Now my oldest is just finishing his second year of college, my middle son is graduating from high school this year, and my youngest son just turned 17 yesterday! Before you know it, your little girl will be graduating too!
Yikes! that reminds me, I will have two college bills this fall!

My best to you! (((Hugs)))

Kathy

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