NSCLC- cisplatin nephrotoxicity - 1246139

drpan78
Posts:3

My 63 year old father is having an adjuvant chemotherapy with 4 cycles of cis-platin ( day 1) + vinorelbine (day 1 and 8).. After the first cycle he had some complications with orthostatic hypotension and a rise of creatinine. Before the chemotherapy his kidney function was normal ( creatinine=0,8). One week after the infusion of cisplatin he had a creatinine of 1,62 and with IV hydration the creatinine levels return back to upper normal limits ( 1,1). Today ( one day before the beginning of the second cycle) he had blood test and a rise in creatinine of 1,41 with a normal urea value were noticed. I have to admit that the previous days he drunk plenty of water because he was afraid of dehydration ( so we cannot assume that he is dehydrated). I called his oncologist and his plan is to continue the same regimen with cisplatin but he says that he may split the cisplatin to two doses ( 1st and 8th day of the cycle).
My questions are:
1. Is the splitting of the cisplatin dose evidence based medicine?
2. Is it safe to continue with cisplatin or is it better to change it with carboplatin?
3. Is the anti-tumor effect of carboplatin the same as cisplatin?

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Reply # - July 30, 2012, 04:48 PM

JimC
Posts: 2753

Hi drpan78,

Sorry to hear that your father is having some trouble with his creatinine levels. Dose adjustments are certainly something that are often required when the side effects of chemo become a problem. As far as kidney issues with cisplatin, Dr. Weiss wrote about some prophylactic measures he employs: http://cancergrace.org/forums/index.php?topic=7718.msg56834#msg56834

The question of whether carboplatin is as good as cisplatin is often debated. Dr. Weiss wrote about this in his post on first line treatment: http://cancergrace.org/lung/2010/04/16/introduction-to-first-line-thera… (scroll down about halfway into the post)

JimC
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Reply # - July 30, 2012, 06:37 PM

Dr West
Posts: 4735

My practice is to routinely split the cisplatin over two days in order to reduce the nausea and renal toxicity. There isn't an extensive amount of study, but that's in part because cisplatin is a 40 year old drug, so no company is incentivized to study the best way to administer it. The available evidence strongly suggests that cisplatin given in lower doses more frequently is not less effective in any way, and if anything it may be more effective, but it's fairer to say it hasn't been exhaustively studied. What I can say is that cisplatin given as one big slug is quite toxic to many people, and I would argue that cisplatin is only a valuable addition if you can administer it without causing terrible renal failure.

In truth, though we think and talk here about the evidence here a great deal, real oncology practice requires some extrapolation from the idealized conditions of evidence-based medicine, because people depart from perfect conditions. I don't think any expert adheres to evidence-based treatments as a limitation, because best treatments do sometimes depart from the very limitated subset of questions that have been addressed by prospective randomized phase III clinical trials. In other words, I think good cancer care requires good judgment and not just formal rules based on phase III trials.

There haven't been great trials of adjuvant carboplatin-based chemo, but the few that have been done have largely demonstrated the same hazard ratio vs. observation that we see with cisplatin-based chemotherapy. Carbo-based trials are fewer and less well powered, but I am happy to recommend that patients who aren't tolerating cisplatin well switch to carbo. It's not as evidence-based, but being more evidence-based with kidney failure is a pyrric victory in my book.

Overall, the data in advanced NSCLC suggest that carboplatin is not quite as efficacious as cisplatin, but close (I'd estimate 90% or more).

-Dr. West

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