For many patients with early stage, resected NSCLC, chemotherapy after surgery may be a strong consideration to minimize the chance of the cancer returning, in which cases, it is often not possible to cure it. Several clinical trials over the past few years have shown benefits from chemo combinations, but which ones would be the leading considerations now?
The first trial that showed a significant benefit of chemo after surgery, the International Adjuvant Lung Trial (IALT abstract), gave any of four chemo regimens, each combining cisplatin with another drug. The most commonly used were etoposide and vinorelbine (also known as navelbine), with the other two choices rarely used in lung cancer these days, at least in the US. Two other trials, one run through the National Cancer Institute of Canada (abstract here), and another done in Italy and presented at international meetings but not yet published, also used cisplatin and navelbine as the only combination used and had better results. So there’s a lot of evidence in favor of cisplatin/navelbine, and it’s a very reasonable and arguably among the best choices in this setting, certainly if you follow the data strictly.
From the setting of metastatic NSCLC, however, we know that the platinum-based two drug combinations that are commonly used are all nearly identical in how effective they are. Cisplatin and navelbine has been compared to other doublets and has been in the same range. One trial in advanced NSCLC (known as TAX 326, abstract here) actually indicated that cisplatin and docetaxel (taxotere) was actually a bit more effective, with a slightly longer overall survival in patients with metastatic disease, than cisplatin/navelbine. That’s a rare case where one doublet outperformed another, but by and large they are remarkably similar in activity and primarily differ in schedule and side effects. So cisplatin/navelbine, cisplatin/taxotere, and cisplatin/gemcitabine (also known as gemzar) would all be very strong considerations. Cisplatin and paclitaxel (taxol) could also be done, but most oncologists don’t tend to use that combination.
The bigger question is whether substituting carboplatin for cisplatin is appropriate. Carboplatin-based doublets generally come out in the same ballpark as cisplatin doublets, and carboplatin is usually considerably better tolerated, so most oncologists favor that in the metastatic setting, where toxicity of treatment is especially important because we can’t realistically plan to cure patients. However, I and many other lung cancer experts believe that cisplatin is slightly superior in activity, and therefore favor using it over carboplatin in the curative setting, despite the greater likelihood of side effects. A few clinical trials and also a recent meta-analysis (cisplatin vs. carboplatin meta-analysis abstract) indicate that cisplatin is associated with modestly better survival in the metastatic setting, and this combined with the fact that all of the data showing a significant survival benefit after surgery used cisplatin makes me favor cisplatin combinations if patients can tolerate it.
There was a very important trial, known as CALGB 9633, that used carboplatin and taxol, after surgery. This was a smaller trial, with 344 patients, less than they had planned, and it included only patients with stage IB disease, who don’t look like they get the same degree of benefit from post-op chemo as stage II or IIIA patients. In the CALGB 9633 trial, the preliminary results (preliminary CALGB abstract) showed a significant benefit vs. no chemo, so most of the lung cancer community felt that chemo with either a cisplatin or carboplatin doublet was fine. However, the updated results (which have only been published as an abstract thus far) showed that the benefits were much less dramatic with longer follow-up. It is possible to consider the CALGB trial as negative or possibly just not positive enough because it was too small to show a significant difference in a group of patients with a good prognosis already. But at the end of the day, the data are not as strong for carboplatin, and the existing evidence suggests that cisplatin is a bit more effective, so that is why I and most other experts in the lung cancer community prefer cisplatin in the adjuvant setting, at least in the patients who are well enough to pursue that approach.
posted by Dr. West @ 11:50 am link to this post
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November 19th, 2006 at 8:14 am
I had stage 1B non-small cell adeno in 2003. At that time, the results of the trial had just come out showing a benefit to adjuvant chemo. My surgeon at the University of Chicago discussed the option with me, and at the time, said that they, as a group, mildly recommended chemo in a case such as mine.
I had three cycles of cisplatin/gemzar, and had some mild side effects, such as thinning hair, weight gain, sob during treatment, stomach and reflux issues.
Except for the hearing loss, which is mild, all of those issues went away very shortly after treatment.
The only thing I regret is that I didn’t get a port or a picc line, and my veins are wasted. It’s especially annoying to me because I don’t let anyone access any veins on my left hand because of previous breast cancer surgery and axillary lymph node surgery.
This makes getting a vein for the contrast for my annual CT really tough.
But, I was willing to do nearly anything to get that extra 5% and now am especially glad to hear that the difference can be up to 15%.
November 19th, 2006 at 10:40 am
Good to have you here talking with us as we approach 2007. As you probably know, the longer we go from the time of your surgery, the lower the chance seeing that cancer recur.
I know many of the oncologists at Univ. of Chicago, so I would have expected you to get state of the art recommendations based on what we were learning about post-op chemo.
November 20th, 2006 at 7:12 am
Thanks for your reply, Dr. West. My surgeon said that 90% of the time, my type of tumor recurs in the first two years if it is to come back at all. Not that the anxiety level doesn’t get almost unbearable at scan time every year, but at least it’s only once a year now.
I did have a consult at the Uuniversity of Chicago with Dr. Ezra Cohen, who recommended chemo in my case, but I did my chemo here in my own city because I live far enough from Chicago to make traveling there weekly very burdensome.
Thank you for this website. This is such a puzzling journey for so many of us, and I for one feel better knowing as much as I possibly can.
January 30th, 2007 at 6:20 pm
Dr. West:
My wife had a lobectomy a year ago for a 2cm tumor that turned out to be an adenocarcinoma with bronchioloalveolar features. She was upstaged to IIIA due to a subcarinal lymph node found to harbor cancer cells by the pathologist.
She was given adjuvant chemotherapy (Cisplatin & Taxotere). After that she had 5 weeks of thoracic radiation. The rationale for this being that it will help reduce the likehood of a local recurrence.
My question is about the addition of radiation to the adjuvant chemotherapy. Is this a common adjuvant regime? Has there been any clinical trials that compare chemotherapy + radiation over chemoterapy in the adjuvant setting?
Thanks again.
Carlos O.
January 31st, 2007 at 3:41 pm
Carlos,
The chemo regimen of cisplatin and taxotere is definitely among the more commonly used and is one of just three that is being included in a national trial comparing post-op chemo to chemo with avastin. Those three regimens are cisplatin/taxotere, cisplatin/gemcitabine, and cisplatin/navelbine, and I would consider any of these to be a great choice. Other doublets may be just as good, but cisplatin-based doublets are better studied after surgery and may give slightly better results. In terms of the value of post-op radiation, there have not been any studies directly comparing chemo with RT to chemo alone. There have been some older studies that suggested that post-operative radiation may be detrimental. On the other hand,some more recent studies where patients received post-op chemo with or without radiation suggested a possible benefit with both. It’s not clear, and right now post-operative radiation is definitely most compelling for patients who had N2 nodal involvement, but it’s just an open question whether to do both or just chemo. Some of my patients who have N2 node involvement after surgery get radiation, but usually after chemo has been completed, because chemo has the more established survival benefit, and doing both together can make it hard to get through the treatment plan.
I suspect that answer is as clear as mud, but we just don’t know whether and how to combine chemo and radiation post-operative.
-Dr. West
February 1st, 2007 at 1:04 pm
Dr. West:
Thanks for the prompt (and clear) reply. It is much appreciated.
I have a follow up question to the following comment of yours in the this topic:
“Some of my patients who have N2 node involvement after surgery get radiation, but usually after chemo has been completed, because chemo has the more established survival benefit, and doing both together can make it hard to get through the treatment plan.”
My question is the following. In your post “Aggressive Chemoradiation for Unresectable Stage III NSCLC: A Double-Edged Sword” you state that “there is a general consensus that overlapping chemo and radiation is associated with better cure rates for this stage of locally advanced NSCLC than doing one followed by the other.” Since concurrent chemo + radiation seems to have better cure rates for stage III, doesn’t it make sense to try it also in the adjuvant setting for N2 disease (instead of the sequential approach) for fit patients? Is there any clinical trial that is comparing sequential vs. concurrent adjuvant therapy for fit N2 resected patients?
I understand that the concurrent adjuvant treatment may be too aggressive and challenging for resected stages I & II, but it seems to me that in resected N2 disease the benefits may outweigh the risks, in particular in fit patients that may tolerate the treatment and benefit from an increased cure rate.
Thanks again.
Carlos
February 1st, 2007 at 2:46 pm
Carlos,
Oh, I like the way you’re thinking! In fact, there is a trial that is in development and I think may potentially get started soon, asking that very question. On the one hand, chemo with concurrent radiation is a little bit more effective than a sequential approach in unresectable disease, but at the cost of quite tough toxicity. When you throw a big lung surgery into the mix, it vaults the challenge even more. The trial that is being done is small and is for patients who have evidence of N2 node involvement after surgery, and is randomizing patients to concurrent vs. sequential chemo and radiation. It is testing the safety and feasibility of these approaches as carefully as possible, while also looking at the survival in the two arms.
You are absolutely right in your observation, which leads to the very question you asked.
-Dr. West