GemTax and Gemcitabine (Gemzar) alone

[Olga]

There is no answer to a question about relevance of using GemTax combination in ASPS. We had a few fairly bad experiences among our patients with this combination but it is unclear if this regimen is ineffective for ASPS at all or the stage of disease in ASPS is usually very advanced when any chemotherapy is given a consideration after all the physical means of destroying the tumor locally unfeasible by different reasons. The incidence of the adverse effects with the GemTax in ASPS patients seems to exceed the usual low-toxicity profile of this regimen.
We have an anecdotal information about the success with Gemzar (gemcitabine) alone. On the former web-site we had a post from the mother of the female patient with the ASPS metastatic to lungs and liver who had been on the clinical trial for gemcitabine alone a few years ago before of the post. In the beginning of the trial this patient had no response to the drug (I guess she had a stable disease because they kept her on the trial) and only after a prolonged (18 month) administration she had her liver metastases and most of her lung metastases regressed and the remaining metastases were stable for a few years at least at the moment of the post. The subject of that post from the mother of the patient was about the possible adverse effect of the desired by the patient pregnancy on the ASPS dormancy. Unfortunately this post and all the previous posts on the former board we had were deleted by Rose from the old ASPS web-site so I have nothing for a proof and I do not have any contact information of the poster so people would be able to contact her oncologist in order to get an advice.

[Fictional]

I found her! Because the medication Gemzar (Gemcitabine) is an approved drug now (available to every oncologist) and there were reports years ago of a young woman with metastatic ASPS who had tumors slough off with it, I started searching for her and I found her - and spoke with her and her mother tonight.

She is 11 years after the initial Dx now and is NED for the last 4 years (no evidence of disease). Sarah's Mom Nancy kept track of all of the medical details and she is going to see if she can have her chart pulled and share the dosing with her. Hopefully this may help others with ASPS. There are several cases of ASPS patients who got worse with the combination of Gemzar + Taxotere, so be aware of this. Also Sarah's dosing of Gemzar NEVER caused immunosuppression. I saw that treatment of other solid tumors often cause immunosuppression so wbc stimulants were added, platelet transfusions etc..

Sarah presented 20 yo with a thigh primary (as large as a fist, wrapped around the femoral artery) - 10 tumors in lungs bilaterally - all about 1 cm. Traditional chemo x 6 (9 hrs/day x 3 days, lost hair 7 days after chemo) ...afterwards 40+ tumors. Heard about the clinical trial at the University of Colorado. Got admitted as an "exception" so her data never included in the clinical report.

Sarah begun Gemzar infusions (over 1 hr) once a week - took on Friday, wiped out weekend (flu-like symptoms), but able to work on Monday. Weekly x 3, 1 week off, then repeated. After the first 7 weeks, no new tumors, after the next 7 weeks fewer tumors, then after 7 weeks more...only 10 tumors remained. I think it's pretty nice that the response occurred fairly quickly.

Off medications - watched some stable metastases...after 4 years only 3 tumors remained (none larger than 1 cm) - removed with thoracotomies...found to be active alveolar soft part sarcoma. It may have been helpful too that Sarah's doctors removed metastases as soon as they got to be about 1 cm. Her primary by its description sounded larger than 5 cm though.

Now Sarah has been NED for 4 years with yearly scans.

Sarah said the experience of Gemzar was like getting a bad flu. She would just start feeling better, then it would be time to get an infusion again...still she was able to work through this. She did have trouble going to school full-time though.

Re: other side effects, Nancy also recalled it helped to give a lot of fluid (6 bags of saline every weekend).

p.s. I found this protocol for Gemzar in the Asco database - wonder if this was the dosing used? Sarah was diagnosed in 1997. This abstract appeared in 1999.

I am also researching Gemzar - I did see pulmonary toxicity can occur - something to be aware of. In the review paper I saw, they said that it was reversible if recognized immediately (characteristic appearance on chest xr) and treated with steroids. There was one young woman with ASPS who had a bad worsening on Gemzar + Taxotere - wonder if she developed this pulmonary fibrosis complication.

------

Gemcitabine in Patients with Sarcoma of Soft Tissue or Bone Resistant to Standard Chemotherapy (Meeting abstract).
Sub-category: Melanoma and Sarcoma
Category: Melanoma and Sarcoma
Meeting: 1999 ASCO Annual Meeting

Abstract No: 2098
Author(s): O Merimsky, I Meller, Y Kollender, G Flusser, J Isakov, M Inbar
Abstract: Background: Metastatic soft tissue and bone sarcomas (STS & BS) are relatively chemo-resistant and incurable malignancies. Short term responses in rates of 30--40% are achieved by limited number of active but toxic drugs. Patients whose diseases are resistant to the standard agents, eventually have nothing else to be offered. Gemcitabine, which is known for its low toxicity profile and activity in relatively chemoresistant diseases, was given to patients with sarcoma of bone or soft tissues, who had failed on standard chemotherapy. Study design: No exclusions were made on the basis of type of sarcoma, metastatic sites, previous chemotherapy or performance status (KPS). All the patients had symptomatic and measurable disease. Life expectancy was >=3 months. Informed consent was signed. Baseline evaluation included history, physical examination, assessment of KPS, QoL questionnaire, data on narcotics consumption, blood tests, documentation of lesions. Induction phase consisted of gemcitabine 1 gr/m[Superscript 2]/w, for 7 w, followed by 1 w rest. If at least disease stabilization or clinical benefit response were reported, maintenance was given (gemcitabine 1 gr/m[Superscript 2]/w, for 3 w, followed by 1 w rest, repeat d29 = d1). Re-evaluation was performed after every 3 cycles. Dose adjustments were performed according to blood counts. Patients: 18 patients (f = 7; m = 11; age 15--62 y; median 36y) were thus far enrolled. KPS ranged between 40--80% (median 60). Symptoms were pain in 17 and respiratory disturbances in 4 patients. The types of sarcomas were alveolar soft part sarcoma in 1, angiosarcoma in 1, chondrosarcoma in 3, leiomyosarcoma in 2, liposarcoma in 2, MFH in 2, osteosarcoma in 6 and Ewing's sarcoma in 1. Results: 13 patients are evaluable for toxicity and response. Toxicity was acceptable, and included myelotoxicity (PLT <50,000/mm[Superscript 3]: 2/13, no bleeding; PMN < 1000/mm[Superscript 3]: 3/13, no fever; Hb < 10 g%: 4/13, blood units were needed), limb edema: 2/13; fatigue: 5/13; ascites: (no cells) 1/13. Clinical benefit response included alleviation of any symptom: 9/13; cough: 2/13 (only 2 eventually had cough); pain: 9/13. Objective responses were minimal to partial in 2/13 (STS: Angiosarcoma, leiomyosarcoma) stabilization in 3/13 (BS). Time to progression was 4--45(+) w, median 8(+)w. Conclusions: gemcitabine is worth-studying in patients with sarcomas, refractory to standard chemotherapy.

[Olga]

O. Merimsky is a well known oncologist from Israel so this is not the study that we are looking for, the problem is that as I recall there were a few gemcitabine regimens evaluated in the clinical trials at that time (doses and type of the administration -fast, slow, drip, bolus etc.) and then they selected some regimen that is used now but it is not necessary the best one for ASPS with its unique slow growing nature.

[jcs2007]

Thanks for posting this info on Gemzar. We had one oncologist that recommended this as an option but we
had another oncologist that was not sure on the effectiveness for ASPS. Since we did not follow through
with Gemzar, I am unsure of the dose and ect...
Thanks for your deligent research and sharing of info!
Blessings,
Cindy

[Fictional]

Unless Olga or anyone else wants to contact Nancy, maybe I'll check in with her this week and find out more about some of the questions we had.

We talked to our regular onc about this. He said Gemzar is usually tolerated very well. The pulmonary toxicity is mainly seen if prior radiation has been given to the chest. He said the doses given for pancreatic cancer (weekly infusions) are not doses that cause immunosuppression.

In a previous post, I made a mistake and said that someone who died from Gemzar + Taxotere had fibrosis - it was probably ARDS - acute respiratory distress syndrome...kind of like a severe allergic reaction. Supposedly Gemzar pulmonary toxicity can be reversible if caught early and treated with steroids. I also don't know if that is a more common complication in older adults than younger adults or children.

[Olga]

In my reading I have seen that severe allergic reaction to Taxotere is not that rarely encountered...

[Fictional]

It seems to me a general principle re: chemotherapy in ASPS is that "more" can mean "less" or worse outcome. ASPS usually is a relatively indolent cancer. If you can be on something relatively non-toxic for a longer period of time, it's better than some big-gun thing that non-specifically kills lots of actively dividing non-cancerous cells.

I went back and looked over the database from the old ASPS site - and as far as I could see there was no other ASPS patient other than Sarah who had Gemzar only. I counted 6 who did Gemzar + Taxotere and 1 who did Gemzar + Yondelis. I think only 1 had a very severe pulmonary reaction (allergic?) to Gemzar+Tax (she died from the toxicity it seems rather than the cancer), the rest were on it but quit when disease continued to progress.

I think you're right, Olga - allergic reactions seem quite frequent in Taxotere (also known as Docetaxel) in one study incidence of grade 3/4 reactions was 65% in the Taxotere arm. Yuck what a drug. Taxotere was developed to be better than doxorubicin - it is an anti-mitotic (cell division) drug that binds microtubules.

[Arch]

A 65% incidence of garde 3/4 toxicity is worrisome. Our doctor told us that Gemzar + taxotere was a standard second line chemotherapy drug for all soft tissue sarcomas, and was relatively well tolerated.We have anyway decided to stay away from chemo for some time until we have surgically removed Sree's lung mets.
He had 3 rounds of AIM before his primary resection.

[Fictional]

Sent Nancy and Sarah Debolt a bunch of questions and they were wonderful and just sent me the following reply:

Gary Debolt <garynnancy@embarqmail.com>
to: 'F'

Sarah and I have been madly acquiring information for you. We got copies of her records from the Torrington hospital the same day she asked for them--a miracle, even for a small hospital. I'll do my best to answer your questions in the order you asked them.

1. Sarah's doctor in Wyoming who administered the Gemzar was not an oncologist, but an internist. His name is Dr. Steven D.Reeb, and he now practices at the only hospital in Cheyenne, Wyoming, Cheyenne Regional Medical Center. He followed the orders of the oncologist at the university of Colorado.

2. The University of Colorado oncologist was Dr. Karen Kelly. She is now the Deputy Director of the University of Kansas Cancer Center in Kansas City, Kansas. Her email address is kkelly@kumc.edu . She was the doctor in charge of the clinical trial being done in 1998-1999. Sarah could not be in the trial because she had had previous chemotherapy. But Dr. Kelly became her oncologist and may have used the information about Sarah anecdotally. (This also is the answer to question #3.)

4. No, Sarah has not had metastases outside the lungs.

5. As I told you on the phone, 'F', the Gemzar protocol was 1840 mg IV each week x 3 wks, off i wk, then on again for three weeks. She did take Inapsine 1cc IV and Ativan 1 mg IV prior to the infusion of Gemzar to quell her anxiety and nausea. I continued saline infusion at home, and Inapsine, Ativan, and Benadryl at home prn. The three courses of Gemzar (18 infusions in all) were the only chemotherapy she has received since.

6. Other than Sarah noting flu symptoms (which were eased once we got up to the six bags of saline over the weekend--her infusions were always on Friday), there have been no long-term consequences of the Gemzar.

7. Sarah has never married and has no children. The doctors did tell her that the likelihood of her being able to have children was very minimal. This may be the reason she has never sought out relationships.

Sarah's primary tumor was in her left upper thigh. She noticed it in August of 1997. She had been working as a hotel maid in Cheyenne during Frontier Days that July, and just thought the bump on her thigh was from hitting furniture. However, within three weeks, the bump was larger and she called me from college to set up a doctor's appointment here in Torrington. The original MRI report states that the primary mass measured "approximately 4 x 4 cm in transverse dimension and approximately 8 cm in longitudinal dimension." She tumor was resected on October 15, 1997 in Denver and had grown to the size of the doctor's fist. It was wrapped around the femoral nerve. In December she started chemotherapy--Ifosfamide4.25 gm with Mesna 4.25 gm IV over 4-6 hours followed by Etoposide for three days. I can't quite make out the doseage for the Etoposide. She received neupogen shots for about five days following the chemotherapy. She received this chemotherapy for five months. The number of lung tumors rose from ten to over forty during that time, so both Sarah and the doctor agreed to stop that chemotherapy.

The gemzar did not start until February of 1999. The doctors truly had very little hope of it working. But at the end of the first seven weeks, we returned to Denver and there were no new tumors. That gave them pause, so they opted for another seven weeks. After that, the tumors were counted at about thirty. So, with a little more hope, they went for another seven weeks. I think after that third course, there were probably ten tumors left. Sarah went to Denver every three months for CT scans and those tumors slowly sloughed off. I believe it was about two years later when one lung tumor grew beyond the 1 cm size, and they resected that tumor. They also took another one which was close to the first. Three or four years later, they resected another lung tumor which had started growing. Since that time, her CT scans show a few places they believe are scar tissue, but they keep watching them closely. She has CT scans once a year, and an open-sided MRI once a year to be sure there is no reoccurance in her bones or muscles.

If you have any other questions, please e-mail us or call. As I told you on the phone, 'K', you & Brock, and your doctors are all in our prayers. Please keep us up-to-date on 'K''s progress.

Best wishes,
Nancy and Sarah

I do have both Nancy and Sarah's phone numbers, but feel funny about posting them on the Internet. Email me if you would like to talke to them by phone.

[sarah'smom]

Sarah and I want to thank 'F' and Olga for working so hard to find Sarah. From the beginning in 1997, Sarah has been quite shy in discussing her cancer and treatment.It was overwhelming, I'm sure. Sarah has used her energy to support "Relay for Life" in our community, and our church is developing a program to assist families of cancer patients with financial expenses as they travel out of town for treatments. Our home, Torrington, Wyoming, is in the southeast corner of Wyoming. We have a regional cancer center 35 miles away in Scottsbluff, NE, one in Cheyenne, Wyoming, and several in Denver, Colorado. Therefore, travel anywherre from that 35 miles to 150 miles to Denver can be necessary and add to the exertion and frustration of family members attempting to deal with the physical, emotional, psychological, and spiritual complications of any cancer. If Sarah's journey, and the details of it, can be of any use to patients and their families, we are so willing to share. Sarah will probably not post, but she will certainly tell me what to say when she wants to! She discovered her primary tumor when she was 19 at the beginning of her sophomore year in college. She is now 31 years old, works as an activity director in our county's longterm care center for fragile and ill elderly. She is compassionate, has an energy level that our family characterizes as equivalent to the Energizer Bunny, and understands the emotional and physical stresses that chronic disease and impending death can bring onto the elderly she serves. Needless to say, her father and I, and her brother and sister, are so proud of her and her contributions. When we first learned of the primary tumor in August of 1997, I went to a co-worker at our Community Hospital to let off my sorrow and distress at the beginning of Sarah's journey. I'll never forget my friends words: "Oh my goodness! God has some great plans for little Sarah!" My friend nailed it! And Sarah nails it every day! Please let us know how we can help you.

[Olga]

Hi, welcome to the board. We are very grateful for your contribution to the common data base of knowledge about possible ASPS treatments - there are so fer of ones that were able to be successful in any way that every bit of the information is priceless.
I still have a question though - and I am sure other people will to, we just need to digest the info you have given to us, speak to the oncologists etc.
The very important question about gemcitabine administration is a regimen - a time (or a speed) of infusion, as it was found that its pharmakinetics and distribution changes a lot under the different regimens used. Can you please verify for us for how long the infusion was given?

[Olga]

I wanted to ask if anyone was able to contact Sarah's clinical trial Dr. Karen Kelly. (She is now the Deputy Director of the University of Kansas Cancer Center in Kansas City, Kansas. Her email address is kkelly@kumc.edu), I sent her an e-mail and our oncologist did the same and we got no answer from Dr. Karen Kelly. We wanted to verify the protocol and the possible significance of the previous chemotherapy that Sarah had before of going on gemcitabine only (documented progression and for how long).

[Fictional]

I haven't tried because we aren't pursuing this at the moment.

If no reply from her by email, just have the doc call her office number. Some clinicians are always in the clinic and answer their pagers (and therefore phone calls) more than emails. Sometimes the clinicians will tell their secretaries that as long as they aren't in rounds, the secretary have them paged to the phone if another doctor is calling...