John,
This is outside of my pay grade. All I can do is quote what NIH says. This is what they say about
docetaxel:
NIH said...
Hepatotoxicity
Docetaxel has been associated with serum aminotransferase (ALT/AST) elevations in up to half of patients, but values greater than 5 times the upper limit of normal (ULN) occurr in less than 2%. Similar rates of alkaline phosphatase elevations and occasional mild bilirubin elevations also occur. The abnormalities are usually asymptomatic, mild and self-limited, rarely requiring dose modification or discontinuation. Despite the frequency of serum enzyme elevations during therapy, clinically apparent liver injury has not been convincingly linked to docetaxel therapy. Because docetaxel is often given with other antineoplastic agents, liver injury arising during therapy cannot always be attributed reliably to docetaxel or to another specific agent. Furthermore, docetaxel in combination with other antineoplastic agents may be associated with reactivation of hepatitis B, increased risk of opportunistic viral infections, sinusoidal obstruction syndrome and sepsis, any of which can cause liver test abnormalities or clinically apparent liver injury.
Outcome and Management
The serum aminotransferase elevations that occur on docetaxel therapy are usually self-limited and do not require dose modification or discontinuation of therapy. There have been no cases of clinically apparent or severe acute liver injury linked to docetaxel therapy in the published literature.
And here's what they say about
carboplatin:
NIH said...
Hepatotoxicity
Mild and transient elevations in serum aminotransferase levels are found in up to one-third of patients taking carboplatin. However, clinically apparent acute liver injury from carboplatin is extremely rare and the characteristics of such injury have not been well defined. ...
Outcome and Management
The severity of liver injury from carboplatin ranges from mild, reversible enzyme elevation to sinusoidal obstruction syndrome with acute liver failure and death. Liver injury from carboplatin is extremely rare. There is likely to be cross sensitivity to liver toxicities of the various platinum coordination complexes and rechallenge after clinically apparent liver injury should be avoided.
So, as far as I can tell, some ALT/AST elevation is common, but large elevation (>5x normal) is not. There is a difference between a biochemical indicator (ALT/AST) and actual clinical damage to the liver. Symptoms of clinical liver damage are things like right upper quadrant pain, hepatic tenderness, weight gain, edema and ascites, and jaundice.
So it seems like your options include:
(1) stop both
(2) stop the carboplatin only (was there a neuroendocrine cancer identified?)
(3) switch from Taxotere to Jevtana
(4) wait another week before the next infusion
(5) lower the dose, and increase frequency to
50 mg/m2 every 2 weeks or
once weekly at a dose of 35 mg/m2(6) continue as is, unless there is a clinically apparent symptom of liver damage
I think you should discuss all those options with your oncologist. Send him those 2 studies on more frequent lower dosing too. Let us know what he says.
- Allen