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One of the challenges of cancer care is that we guide our treatments by what clinical trial evidence tells us is best for particular patient populations. However, trials exclude patients who have significant medical issues other than cancer. So what do you do for patients who have lung cancer but also have common medical problems like compromised kidney function or pre-existing numbness and tingling (neuropathy) from diabetes or vascular disease? A purist in evidence-based medicine would say that patients who don't have good kidney function or who have other medical problems that would exclude them from the trials of our standard treatments can't get treated, but fortunately most oncologists are more flexible than that. What's the right way to proceed? The answer is that it falls to best medical judgment. But can we be more specific than that?
In the setting of renal insufficiency, which is common as patients get older, as well as being a result of years of high blood pressure or diabetes, we need to substitute out the treatments that are most threatening to kidney function worsening. Specifically, this means avoiding the particularly kidney-threatening cisplatin, considering avoiding carboplatin (or perhaps giving it and carefully monitoring kidney function and dropping if it kidney function worsens, and then substituting non-kidney damaging agents instead). If kidney function is only minimally impaired, it may be very acceptable to give carboplatin plus a taxane: Taxol (paclitaxel), Abraxane (nab-paclitaxel), or Taxotere (docetaxel)), Gemzar (gemcitabine), Navelbine (vinorelbine), or Alimta (pemetrexed). An alternative, and the leading one if kidney function is quite compromised or gets worse on carboplatin-based chemo, is to give a nonplatinum doublet, which basically means pairing two drugs for lung cancer that are more commonly partners for cisplatin or carboplatin. Common nonplatinum doublets include Gemzar/Navelbine or Gemzar with one of the taxanes. About 15 years ago, there was a significant hope that these agents might turn out to be an improvement from platinum-based doublets, with comparable or slightly superior efficacy and improved tolerability. That didn't turn out to be the case: the nonplatinum doublets were typically of the same or very slightly lower efficacy, and the same or slightly better tolerability. Overall, they were a lateral move and never took hold as a leading choice, but they are certainly a fine choice and arguably the ideal one for people with limited kidney function.
Then there's the case of patients with peripheral neuropathy. The taxanes and especially Taxol are the worst offenders here, as is cisplatin, and Navelbine can also worsen neuropathy. Here, we commonly favor carboplatin with a less neuropathy-inducing partner drug, so Gemzar is often a leading choice, or Alimta for a non-squamous lung cancer.
It's also reasonable to consider single agent chemotherapy, though several recent trials have shown that carboplatin doublet chemotherapy is associated with better outcomes as first line treatment than single agent chemo, even in patients with a marginal performance status. But it's certainly reasonable to consider single agent chemo in individual patients with significant organ compromise, or simply in patients who are particularly wary about significant side effects.
Though there are certainly other problems that merit individual treatment recommendations, these are among the most common ones. In the end, it still comes down to individualized judgments and considerations of the circumstances of the particular patient.
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Hi elysianfields and welcome to Grace. I'm sorry to hear about your father's progression.
Unfortunately, lepto remains a difficult area to treat. Recently FDA approved the combo Lazertinib and Amivantamab...
Hello Janine, thank you for your reply.
Do you happen to know whether it's common practice or if it's worth taking lazertinib without amivantamab? From all the articles I've come across...
Hi elysianfields,
That's not a question we can answer. It depends on the individual's health. I've linked the study comparing intravenous vs. IV infusions of the doublet lazertinib and amivantamab...
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