what's that???different platinum compounds cancausedifferent degrees of hearing loss

Lani · 12-31-2008, 10:41 AM

Pharmacokinetics May Explain Differences in Cisplatin and Oxaliplatin Ototoxicity
(Eureka News Service)
More cisplatin enters the inner ear in an animal model than oxaliplatin. The difference may explain why cisplatin treatment in humans can lead to hearing problems while oxaliplatin rarely does.
The amount of cisplatin a patient can tolerate is often limited by hearing damage induced by the drug, referred to as ototoxicity. Oxaliplatin is not frequently associated with the problem, despite the fact that both drugs are platinum compounds.
To find out why the difference exists, Victoria Hellberg, M.D., at the Karolinska Institutet in Stockholm, and colleagues measured the amount of cisplatin and oxaliplatin that reached the cochlea in guinea pigs following intravenous dosing of each drug.
The total platinum concentration in the cochlea was more than five-fold higher with cisplatin than with oxaliplatin following intravenous injection. The perilymphatic drug concentration was also higher in the cisplatin-treated animals than in those exposed to oxaliplatin.
"The differences in cochlear kinetics and cellular uptake that we found in the hearing end organ are sufficient to explain the difference in ototoxicity between cisplatin and oxaliplatin," the authors conclude.

OPEN ACCESS: Cisplatin and Oxaliplatin Toxicity: Importance of Cochlear Kinetics as a Determinant for Ototoxicity
(Journal of the National Cancer Institute)
Background: Cisplatin is a cornerstone anticancer drug with pronounced ototoxicity, whereas oxaliplatin, a platinum derivative with a different clinical profile, is rarely ototoxic. This difference has not been explained.
Methods: In HCT116 cells, cisplatin (20 μM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold), to 3.1-fold induction (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging from 9.3-fold (95% CI = 8.8- to 9.8-fold), to 5.1-fold (95% CI = 4.4- to 5.8-fold). A guinea pig model (n = 23) was used to examine pharmacokinetics. Drug concentrations were determined by liquid chromatography with post-column derivatization. The total platinum concentration in cochlear tissue was determined by inductively coupled plasma mass spectrometry. Drug pharmacokinetics was assessed by determining the area under the concentration-time curve (AUC). Statistical tests were two-sided.
Results: In HCT116 cells, cisplatin (20 μM)-induced apoptosis was reduced by a calcium chelator from 9.9-fold induction (95% confidence interval [CI] = 8.1- to 11.7-fold to 3.1-fold induction) (95% CI = 2.0- to 4.2-fold) and by superoxide scavenging (from 9.3-fold, 95% CI = 8.8- to 9.8-fold, to 5.1-fold, 95% CI = 4.4- to 5.8-fold). Oxaliplatin (20 μM)-induced apoptosis was unaffected by calcium chelation (from 7.1- to 6.2-fold induction) and by superoxide scavenging (from 5.9- to 5.6-fold induction). In guinea pig cochlea, total platinum concentration (0.12 vs 0.63 μg/kg, respectively, P = .008) and perilymphatic drug concentrations (238 vs 515 μM x minute, respectively, P < .001) were lower after intravenous oxaliplatin treatment (16.6 mg/kg) than after equimolar cisplatin treatment (12.5 mg/kg). However, after a non-ototoxic cisplatin dose (5 mg/kg) or the same oxaliplatin dose (16.6 mg/kg), the AUC for perilymphatic concentrations was similar, indicating that the two drugs have different cochlear pharmacokinetics.
Conclusion: Cisplatin- but not oxaliplatin-induced apoptosis involved superoxide-related pathways. Lower cochlear uptake of oxaliplatin than cisplatin appears to be a major explanation for its lower ototoxicity.

Believe51 · 12-31-2008, 11:23 AM

Hmmmm, interesting. I will have to keep this in mind if we need to go this route in the future. Ed is already hard of hearing, then chemo, WBR and Gamma Knife close to ear area. Right now we are planning on going to a sign language class so we can communicate if need be.

Rich66 · 12-31-2008, 01:04 PM

hmmm. I remember my mom's hearing seemingly worse after that 1 infusion of Taxol in late September. Seems better now. Is this a know issue with some chemos?
Belief51,
I'm impressed by your proactive measures!

hutchibk · 12-31-2008, 01:29 PM

A friend of mine (not BC, but mets from another cancer) had horrible ear ringing after cisplatin and then several months later, carboplatin. He always asked me if I ever had it and I said only mildly but it went away for me... this is interesting.

I wonder if brain rads or herc/tykerb combo cause weirdness in the ears, as I have had varying degrees of mild roaring, popping, ringing, and clogging - ever since I had my dizzy episode back in November. These mild symptoms seem to go away and then sporatically appear from time to time.

Hopeful · 12-31-2008, 04:24 PM

I developed ringing in the ears shortly after starting on Femara. I spoke to the company and they documented my symptoms as part of their after market research. I think many different types of cancer treatments are toxic to the ears.

Hopeful

StephN · 12-31-2008, 04:42 PM

"EUREKA" is right!

When I was offered Cisplatin (before adjuvent Herceptin was available) for my aggressive disease, this was not one of the side effects mentioned. That was a 3rd opinion I went to, and, who knows, I may have done better against the cancer with Cisplatin than with the Adriamycin.

It is getting to be EVEN MORE boggling to the mind which treatment to accept with all they now know. But then Herceptin takes away a lot of that for the treatment beginner.