Cisplatin or Carboplatin with Alimta for First Line Therapy - 1259020

aschweig
Posts:25

My 61-yo Asian mother-in-law has been diagnosed with Stage 4 NSCLC -- muscinous adenocarcinoma, poorly differentiated; EGFR-neg, ALK-neg.

She is about to start treatment with Alimta. Based on the following clinical trial, I've advised her to choose Cisplatin because it had the lower cumulative incidence of grade 3/4 toxicities (roughly half that of Carboplatin)

A randomized phase II study of pemetrexed in combination with cisplatin or carboplatin as first-line therapy for patients with locally advanced or metastatic non-small-cell lung cancer.

However, I am keenly aware that this does not agree with the bulk of anecdotal evidence -- even the anecdotal reports from doctors. Our oncologist will switch if our initial choice of platinum therapy tuns out to be too toxic.

My questions:
- I only have access to the abstract which mentions grade 3/4. Does cisplatin have a significantly higher incidence of grade 4 toxicities, specifically?
- Was there something about the trial design that reduced adverse events with cisplatin?
- Could someone direct me to a study of no less relevance that would validate people's expectation that carboplatin is better tolerated for this situation?

Thanks.

aschweig

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Reply # - September 5, 2013, 09:18 PM

Dr West
Posts: 4735

I can't point to a specific trial, but you're looking at a small trial that is really of minimal significance compared with decades of experience with these agents. I know of no oncologist who considers cisplatin to be more tolerable or even comparably tolerable to carboplatin, which is associated with more lab-based abnormalities that are usually not "felt" by a patient, but cisplatin is associated with far, far more nausea, vomiting, risk of kidney damage, hearing loss, and peripheral neuropathy. I think it's very reasonable to give cisplatin and interpret the efficacy as perhaps marginally greater with cisplatin, but nobody who has treated a significant number of people with both agents favors cisplatin for its better tolerability.

-Dr. West

Reply # - September 6, 2013, 12:26 PM

carrigallen
Posts: 194

I reviewed the article and will reproduce select portions of it for you below:

Pemetrexed Plus Cisplatin
For patients treated with pemetrexed plus cisplatin, the most commonly reported drug-related grade 3/4 hematologic toxicity was neutropenia (11 patients [16.9%]). Grade 4 neutropenia was reported in 1 patient; 10 patients had grade 3 neutropenia. Other drug-related grade 3 hematologic toxicities included anemia (5 patients [7.7%]) and thrombocytopenia (2 patients [3.1%]). No other grade 4 hematologic toxicities were reported nor was febrile neutropenia observed (Table 3). The most commonly reported drug-related nonhematologic toxicities were grade 3 nausea (3 patients [4.6%]), followed by vomiting and fatigue (2 patients each [3.1%]) (Table 3). Seven (10.8%) patients received at least 1 transfusion of packed red blood cells. One death (from multiple organ failure) occurred that was considered related to the study drug.

Pemetrexed Plus Carboplatin
For patients treated with pemetrexed plus carboplatin, the most commonly reported drug-related grade 3/4 hematologic toxicity was neutropenia (17 patients [26.2%]). Other drug-related grade 3/4 hematologic toxicities included thrombocytopenia (11 patients [16.9%]) and anemia (7 patients [10.8%]) (Table 3). Febrile neutropenia was not observed. The most commonly reported nonhematologic toxicities were grade 3 nausea (5 patients [7.7%]), followed by fatigue, anorexia, and urinary tract infection (2 patients each [3.1%]) (Table 3). Sixteen (24.6%) patients received at least 1 transfusion of packed red blood cells; 4 also received thrombocytes. Two deaths (from hemorrhage and pancytopenia) occurred that were considered related to the study drug.

Reply # - September 6, 2013, 12:37 PM

carrigallen
Posts: 194

Remember the toxicities with carboplatin are usually 'on paper', not usually felt by the patient. These 'paper toxicities' of carboplatin are outlined in this German trial - neutropenia, moderate low platelets, moderate anemia, etc. In contrast, cisplatin toxicities, like Grade 2 vomiting or Grade 2 neuropathy are horrendous for the patient, but don't even get reported as 'serious' events unless they are Grade 3 or higher. Cisplatin can cause some alopecia as well.

Remember in Germany they use less growth factors than USA, so carboplatin neutropenia is expected to happen more often there than in most community practices in the USA. Hope this helps.

Reply # - September 6, 2013, 10:36 PM

aschweig
Posts: 25

Thanks everyone for your thoughtful replies.

Dr Creelan -- can you expand on the "growth factors" -- I always thought a treatment was a treatment -- do you mean pre-medication?

From the abstract above:
- 65 Patients in each arm.
- Mostly men in each arm. (could this have some impact?)

Pemetrexed + Cisplatin:

Total incidence of grade 3/4 toxicities: 16.9 + 7.7 + 3.1 + 4.6 = 32.3% of all 3/4 toxicities
Also: 1 death; 7 patients got 1 or more transfusions; 1 patient with grade 4 toxicity

Pemetrexed + Carboplatin:
Total incidence of grade 3/4 toxicities: 26.2 + 16.9 + 10.8 + 7.7 = 61.6%

Also: 2 deaths; 16 patients got 1 or more transfusions.

I agree that most of the carboplatin toxicities are on paper. However, the incidence of transfusions suggests that some of the "on paper" toxicities have real-world consequences.

I also found the following comparing cisplatin + alimta and carboplatin+alimta:.

Phase 2 Study of Pemetrexed Plus Carboplatin, or Pemetrexed Plus Cisplatin with Concurrent Radiation Therapy Followed by Pemetrexed Consolidation in Patients with Favorable-Prognosis Inoperable Stage IIIA/B Non-Small-Cell Lung Cancer. -- Incidence of grade 4 toxicities seems to be higher with carboplatin.

Pemetrexed plus cisplatin or pemetrexed plus carboplatin for chemonaïve patients with malignant pleural mesothelioma: results of the International Expanded Access Program. -- Higher incidence of grade 3/4 neutropenia with carboplatin.

Pemetrexed plus carboplatin or cisplatin as neoadjuvant treatment of operable malignant pleural mesothelioma (MPM). -- Supports carboplatin as less toxic; 51 patients.

I find it odd that something so obvious to practitioners isn't a common finding in trial data.

Thanks again for all your help!

Reply # - September 7, 2013, 09:09 AM

catdander
Posts:

Here's an explanation of growth factor,
http://cancergrace.org/cancer-treatments/2012/04/13/hematopoiesis-and-g…

This quote is one of many similar statements from our faculty over the years on Grace, "The question of whether to use cisplatin or carboplatin in our 'platinum-based chemotherapy doublets' that are the most common treatment for the first-line treatment of NSCLC has been a smoldering debate in lung cancer for more than a decade." http://cancergrace.org/lung/2007/08/19/cis-vs-carbo-for-adv-nsclc/

This link provides the results of a search carboplatin vs cisplatin because your questioning is the same hotly debated question that's been circulated for years. http://cancergrace.org/search-results?q=carboplatin%20than%20cisplatin

Don't miss our search engine just because microsoft, google, and apple can't play together for all their competing. In other words you may need to log off before accessing search results on Grace depending on the type of browser you're using.

All best,
Janine

Reply # - September 7, 2013, 10:06 AM

aschweig
Posts: 25

Hi Janine,

I am aware that there is a debate between cisplatin (thought to be marginally more effective) and carboplatin (more well tolerated.) However, I cannot find published reports that substantiate that carboplatin has any advantage at all in terms of grade 3/4 toxicities. (well, so far, only one small study.)

I now suspect that the real benefit of carboplatin may be that is has fewer non-life threatening but nonetheless psychologically disturbing side-effects.. at the expense of a higher proportion of grade 3/4 toxicities and incidence of blood transfusions.

Thanks for the information of the growth factors. I did not understand that these were regularly administered during treatment with Carboplatin.. I'll have to have a talk with the oncologist.

Thanks again!

Reply # - October 15, 2013, 05:20 PM

gia77
Posts: 1

I was dx'd with stage 3a (late stage2) mod differientiated adeno of the R lung 2.8 cm centrally located tumor, 2.9 cm paratracheal lymph node in may 2013. As a first line of defense, I had 4 cycles of chemo alimta/cisplatin first 2 cycles, alimta/carboplatin the last 2 cycles. I took no supplements during tx other than folic acid. CT/pet fusion follow up concluded lymph node resolution and no hypermetobolic activity seen anywhere, soft tissue thickening noted. Persistent dry cough of 1 year as only symptom terminated after first tx.

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