Many patients get IL-2 as an outpatient treatment. In fact, far more get some version of outpatient IL-2 than get high dose IL-2. There are many different versions of outpatient IL-2 treatment, but almost all deliver the IL-2 by subcutaneous injection, at much lower doses than for high dose IL-2, but for a longer period. Outpatient IL-2 is very often combined with other drugs, especially Interferon, but also many others. There is no question that outpatient IL-2 can give remissions and long ones at that, so it definitely offers real hope. Whether it is the best treatment is another question.
Outpatient IL-2 is a complex subject because IL-2 is often given in combination with any of an increasingly large number of other drugs, and because the doses and schedules of administration are tremendously variable. Because of the size of the topic I can’t possibly cover every variation and combination. Instead I concentrate on popular outpatient treatments as well as any treatments which look particularly promising.
High Dose as the “Gold Standard”
My approach is to consider the long term survivals from high dose IL-2 to be the “gold standard” and to ask whether there is evidence to suggest any outpatient IL-2 treatment is as good or even better. If there is doubt, then absent something to indicate a chance for an actual improvement in efficacy, I advise sticking with the high dose. If you don’t qualify for high dose IL-2 but could take outpatient IL-2, then this logic doesn’t apply (see below) and some form of outpatient IL-2 may then be your best bet.
Outpatient is Popular (in part) Because it’s Easier to Give
Although many more patients get outpatient IL-2 than high dose, I believe this isn’t primarily because of any strong evidence that outpatient IL-2 is actually more effective than high dose IL-2. Instead, I think relative ease of managing the treatment and cost considerations are the primary reasons. Giving high dose IL-2 is a specialized skill and inpatient treatment is very expensive. Very few centers give high dose IL-2. Factors I think are secondary, but still real, are milder side effects for outpatient IL-2, and that some patients can take outpatient IL-2 who can’t safely be given high dose.
All of this is independent of the evidence for efficacy. In the end, what may amount to mere convenience is a poor basis for making a treatment decision if your aim is to maximize the odds of long-term survival. Instead, you can confront the actual evidence to make an informed decision. If you decide on high dose IL-2 or a different version of outpatient IL-2 than what your doctors are proposing you can, and may need to, actively seek out and obtain your chosen treatment from other doctors.
Milder Side Effects as a Short Term Tactical Advantage
Outpatient IL-2 has milder side effects than high dose “immuno-shock therapy” – but it’s still no picnic with flu like symptoms, nausea, vomiting and fatigue of variable intensity in most patients. Moreover, outpatient treatments are prolonged so while you might not be as sick, you’ll be sick for longer. Some patients are able to maintain a somewhat normal life during outpatient IL-2 – some are even able to work. Many others are quite sick during the treatment. Whether milder side effects but for a longer period of time is actually an advantage, depends on your preferences as well as how sick outpatient IL-2 makes you – something you can’t know in advance.
What is important is to consider that any advantage here is short term and tactical compared to the long term goal of cure. I don’t think it’s be worth it to trade off long term efficacy for this short term tactical advantage – if indeed it is an advantage. A better reason to choose an outpatient treatment would be results suggesting that treatment has better long term results than high dose IL-2.
If You Don’t Qualify for High Dose IL-2
If you don’t qualify for high dose IL-2 but could take outpatient IL-2, then there’s no point in comparing results to high dose IL-2 and the milder side effects are more than a mere tactical advantage – they may permit you to take the therapy.
With respect to Interferon, little or no long term benefit has been seen and I do think long term benefit is definitely possible with outpatient IL-2 (whether as likely as with high dose or not), therefore I would certainly advise outpatient IL-2 in some form over Alpha-Interferon.
Judging the Evidence for Outpatient IL-2 Treatments
Evidence for outpatient IL-2 treatments is usually in the form of reports of response to the treatment (tumor shrinkage). A better response rate than high dose’s 15-20% for some version of outpatient IL-2 could signal an improved treatment, but it’s dangerous to rely on response rates alone because there is a big risk responses might not last. When IL-2 is combined with other drugs some of the responses may be transient responses due to the other drugs, and these drugs typically don’t give durable responses by themselves. It may also simply be that responses to lower doses of IL-2 don’t last as long, so it’s critical to consider the durability of responses. It’d would take years to prove long term durability equal to that for high dose IL-2, where responses are ongoing after well over a decade. Given the meager (but real) rate of long term benefit with high dose it’s not reasonable to demand that kind of follow-up. Instead, it seems fair to look to strong signs the new treatment will prove superior in the end. Specifically, if the responses are holding so far and the rate of relapse is declining (which should lead to flattening of the survival curve), there would be good reason to hope the new treatment is better. In fact it was just this kind of evidence, a number of apparently durable responses, which convinced me back in 1989 that high dose IL-2 was worth trying over the then standard treatment, Interferon (See my article The Hint for the details).
Outpatient IL-2 and Innovation
Because so few centers give high dose IL-2, and because it’s already such a difficult treatment, little work on improving high dose treatment is being done. Instead, most attempts to improve on IL-2 involve new outpatient combination therapies, so it’s likely that any real advance in IL-2 treatment will come in outpatient therapy. It would be a big mistake to simply dismiss all outpatient treatment out of hand. Instead, look for anything new and truly exciting in outpatient IL-2 treatment.
Specific Outpatient IL-2 Therapies
IL-2 Alone or with Interferon
These are both popular therapies and there are results from randomized trials comparing to high dose IL-2 for both of them, and in each case the results, while not completely definitive, favor the high dose treatment. Consequently, I think those who can should take high dose over either of these treatments. Keep in mind that there are variations in even these outpatient treatments, but I know of none with convincing evidence of equality to high dose IL-2. I cover the randomized trials in detail in my article, Important Randomized Trials With High Dose IL-2.
The Atzpodien Regimen: IL-2, Interferon, and 5-FU (and beyond)
This treatment is commonly used in Europe. It is one of the best studied outpatient regimens and can definitely produce long term results. I don’t favor it over high dose IL-2, but I think adding a fourth drug called 13-Cis-Retinoic Acid merits consideration if high dose is not an option. I also think the Atzpodien regimen or that regimen plus 13-Cis-Retinoic is close enough, with enough long term results to be a very reasonable choice where high dose IL-2 can’t be obtained. See The Atzpodien Regimen and Beyond for all the details.
New and Experimental
IL-2 + Thalidomide is of particular interest. My section on New, Promising, and Experimental therapies covers this, and any other promising new IL-2 treatments, in detail.
This CancerGuide Page By Steve Dunn. © Steve Dunn
Page Created: February 10, 2003, Last Updated: February 3, 2004