1st Line Treatment confusion

[rox5407]

Hi Dr. Goodman,

I am so grateful for this forum and want to thank you for what you are doing here. It is so hard to find accurate and expert information out there with this very scary disease.

I am 38, was diagnosed with Stage IIIC OVCA and had optimal debulking surgery on 4/29/10. I am on my 7th round of carbo/taxol (was originally scheduled for 6 but had a partial bowel obstruction causing a temporary rise in CA125). They also thought that Chemo #6 could possibly not have been properly absorbed and that the IP port caused problems, possibly infection. All that resolved, my CA125 just before this 7th chemo is at 13. This is to have been my last treatment.

I am wanting to request one more chemo just to get it into single digits and was told by another doctor from Northwestern (in an over the phone consult) that he was reluctant to stop 1st line chemo as long as the CA125 continued to go down and then would often do one or two more after that. This particular doctor at Northwestern believes that Hexalen is a good choice of drug once you are finished with traditional chemo regimen.

I would love to know your opinion on continuing chemo as long as there is a continued reduction in CA125 numbers, as well as your thoughts on Hexalen.

Thanks in advance,
Roxanne Cousins

[Annekathryn Goodman, M.D.]

Hi Roxanne
hexalen is an effective chemo drug that has been used in recurrent ovarian cancer.
I do not think there is much experience with it for maintenance chemo
it is an oral agent
I got this from a nice site:http://www.drugs.com/pro/hexalen.html#splSectionAdverseReactions

ADVERSE REACTIONS
Gastrointestinal

With continuous high-dose daily Hexalen® capsules, nausea and vomiting of gradual onset occur frequently. Although in most instances these symptoms are controllable with anti-emetics, at times the severity requires Hexalen® capsules dose reduction or, rarely, discontinuation of Hexalen® capsules therapy. In some instances, a tolerance of these symptoms develops after several weeks of therapy. The incidence and severity of nausea and vomiting are reduced with moderate-dose administration of Hexalen® capsules. In 2 clinical studies of single-agent Hexalen® capsules utilizing a moderate, intermittent dose and schedule, only 1 patient (1%) discontinued Hexalen® capsules due to severe nausea and vomiting.

Neurotoxicity

Peripheral neuropathy and central nervous system symptoms (mood disorders, disorders of consciousness, ataxia, dizziness, vertigo) have been reported. They are more likely to occur in patients receiving continuous high-dose daily Hexalen® (altretamine) capsules than moderate-dose Hexalen® capsules administered on an intermittent schedule. Neurologic toxicity has been reported to be reversible when therapy is discontinued. Data from a randomized trial of Hexalen® capsules and cisplatin plus or minus pyridoxine in ovarian cancer indicated that pyridoxine significantly reduced neurotoxicity; however, it adversely affected response duration suggesting that pyridoxine should not be administered with Hexalen® capsules and/or cisplatin (1).

Hematologic

Hexalen® capsules causes mild to moderate dose-related myelosuppression. Leukopenia below 3000 WBC/mm3 occurred in <15% of patients on a variety of intermittent or continuous dose regimens. Less than 1% had leukopenia below 1000 WBC/mm3. Thrombocytopenia below 50,000 platelets/mm3 was seen in <10% of patients. When given in doses of 8-12 mg/kg/day over a 21 day course, nadirs of leukocyte and platelet counts were reached by 3-4 weeks, and normal counts were regained by 6 weeks. With continuous administration at doses of 6-8 mg/kg/day, nadirs are reached in 6-8 weeks (median).

Data in the following table are based on the experience of 76 patients with ovarian cancer previously treated with a cisplatin-based combination regimen who received single-agent Hexalen® capsules. In one study, Hexalen® capsules, 260 mg/m2/day, was administered for 14 days of a 28 day cycle. In another study, Hexalen® capsules, 6-8 mg/kg/day, was administered for 21 days of a 28 day cycle.

ADVERSE EXPERIENCES IN 76 PREVIOUSLY TREATED OVARIAN CANCER PATIENTS RECEIVING SINGLE-AGENT Hexalen® CAPSULES Adverse Experiences % Patients
Gastrointestinal
Nausea and Vomiting
     Mild to Moderate
     Severe
Increased Alkaline Phosphatase
33
     32
     1
9
Neurologic
Peripheral Sensory Neuropathy
     Mild
     Moderate to Severe
Anorexia and Fatigue
Seizures
31
     22
     9
1
1
Hematologic
Leukopenia
     WBC 2000-2999/mm3
     WBC <2000/mm3
Thrombocytopenia
     Platelets 75,000-99,000/mm3
     Platelets 60 mg%
7
9
     5
     3
     1


Read more: http://www.drugs.com/pro/hexalen.html#splSectionAdverseReactions#ixzz120LTfnvH

[rox5407]

Dr. Goodman,

Thank you so much for getting back with me so quickly. It seems that it is just so hard to get access to information when it comes to OVCA, and I really appreciate you sharing yours through this forum.

My onc has not recommended a second look surgery, although I wish they would so this. It seems as if it might improve some of our odds. I have gotten CT scans, but to my knowledge not PET scans (though I was told they use a combination here at Sloan), so a little confused about that, and assume PET scans are more accurate?

I also wondered if you had any thoughts you might share on Hexalen?

Again, thank you so, so much for what you are doing here!

Roxanne Cousins

[Annekathryn Goodman, M.D.]

Dear Roxanne
thank you for your question. We have all wondered about what is the right number of treatments. There is no wrong answer here.

It has fallen out of favor, but it used to be standard to perform a second look surgery after 6 cycles of chemo to decide about further chemo. That surgery involved a big laparotomy and lots of biopsies . If cancer was identified, another 6 cycles of chemo were given.
if no cancer was found, we would stop. This was in the 1980's and 1990's

Then people started trying to do the same thing with laparoscopy instead of subjecting women to a huge incision.But laparoscopy is terribly inaccurate.You just cannot get underneath adhesions, behind the liver, and so forth.
And no one could prove that 12 was better than 6 cycles .
And by the new century, off a clinical trial, the practice stopped.

So now the standard is 6 or 8 and then we wait until there are signs of recurrence
it is not very satisfying is it?

there have been two recent studied looking at giving maintenance therapy after carbo taxol
one with a year of taxol which showed a longer time to recurrence but terrible neuropathy and lower quality of life

and the recent one with avastin (bevicizumab) which shows a 3.7 month increase progression free interval but no survival data.

hard to know what to do with that.

SO for you, there are two ways to look at this CA 125 of 13
it could be that that is where you live and it will never be lower and that has nothing to do with ovarian cancer presence

or it could be that the level reflects a clone of cells that is persistent and chemotherapy resistant.

if the CA 125 is because of of # 1 - getting more chemo does not make sense and increases permanent neuropathy

If reason # 2 is true, then you should not get more carbo taxol because what is there is resistant to that chemo and it is time to think of a clinical trial and a different agent.

how to sort that out? PET scan? or laparoscopy or another laparotomy or just wait and see with serial CA 125 blood tests?

these are the issues to discuss with your oncologist

best wishes