Lessons in Supportive Care VI: Inpatient vs. Outpatient Therapy
By Thomas J. Smith, MD
Case 1: Your practice of four people has one doctor who always hospitalizes patients for 24 hour infusions of taxol, even if they have been receiving it for six months. Some of the patients are starting to complain; you are losing office revenue from the chemotherapy; and for your capitated patients, the expense of hospitalization is coming out of your salary. The doctor says, "I have always done it this way, and I haven’t seen data it is wrong." What should you do?
Case 2: The mother of a friend has non-small cell lung cancer and is hospitalized for four days to receive etoposide and cisplatin 100mg/m2. When she asked why hospitalization was needed, the doctor said it was to protect her kidneys and that he "always" did it that way. (Editorial comment: This same doctor "always" gives cisplatin and etoposide. When shown the recent trial data showing superiority of cisplatin and paclitaxel or vinorelbine to his favorite, he said those regimens were too toxic. Then, when the patient progressed on etoposide, with rapidly failing performance status, he switched to cisplatin and vinorelbine. Then, when the patient progressed on vinorelbine, with worse performance status, he switched to paclitaxel and radiation. He never did refer to hospice, or discuss her imminent death, even with the patient on her death bed. Go figure.)
With $115 billion being cut from Medicare over the next five years, something has to go. A critical look at why we hospitalize patients for chemotherapy could lead to a potential gold mine, if we could forego hospitalizations.
Why hospitalize people for chemotherapy?
When I started hematology/oncology training in 1984 (although I first caught the bug in 1977), we always hospitalized patients for chemotherapy. The available anti-emetics were Neanderthal, and insurance plans were as flush as the ferns that fed the dinosaurs. Local practice variations abounded: "Son, we always give cisplatin over 1, 4, 6, or 24 hours." It seemed right, and there was no compelling reason to change. Many of us never moved beyond this stage.
There is surprisingly little evidence that regimens must be given in the hospital except for patient or doctor convenience. Oh, occasionally the odd insurer will only pay for inpatient or intravenous chemotherapy, or a patient’s co-payment will be much higher with oral therapy, but that is becoming more rare.
How commonly is therapy being given as inpatient when it could be done as outpatient? I have not been able to come up with data. But I have listed some "target" regimens for shifting below.
Target therapy regimens
RegimeCurrent site Reason not to give as outpatient
VAD IP ?
cisplatiIP, OP hydration, urine output?
ESHAP IP complicated
maintain urine output
paclitaxel IP, OP fear of anaphylaxis
? better efficacy
Your choice here
*IP = Inpatient
Can treatment be given safely as an outpatient?
That question seems relatively straightforwardyes, depending on the treatment and the patient. But the level of knowledge about IP vs. OP treatment is sadly lacking. It is not very exciting to do a trial of OP VAD vs. IP VAD, compared to son of doxorubicin vs. doxorubicin. Of the treatments listed above, there is no clear cut evidence for superiority of IP vs. OP for any regimen, or vice versa.
For VAD, there is no hydration or intense anti-emetic regimen. We and many others have given this as an outpatient regimen.
For cisplatin, nearly all of us have moved to outpatient administration (except the doctor above). There is ample evidence of safety, based on experience, when cisplatin is given with mannitol and fluids. The best recent review is in a "throwaway" (Catalano RB. What are the guidelines of mixing and administering cisplatin? Oncology News International 1997;6(7):44-45). Catalano makes several points: 1) separate regimens into low, medium, and high doses; 2) give a standard hydration package for each; and 3) routine use of electrolyte solutions and diuretics are not needed except to maintain urine flow. He goes on to give very specific directions; the cisplatin is given at 1 mg/mL at a rate of 1 mg (or 1 mL) per minute. I have put his recommendations into a table since they are so simple and practical and correspond to what our pharmacists say.
Guidelines for mixing and administering cisplatin
Cisplatin dose mg/m2 Hydration pre/post
£ 50 200 NS ´ 2 hrs
250 ´ 1
50-74 500 ´ 2
500 ´ 2
75-100 500 ´ 2
1500 mL of 5% mannitol @
There is no published experience with outpatient ESHAP given for recurrent lymphomas. However, our division has evolved a workable regimen that meets approval of all members, including experts on the pharmacology of cytarabine and cisplatin. (To be honest, we could not find a compelling rationale for continuous infusion therapy.) This seems to work for quick cytoreduction prior to high-dose chemotherapy, is as well tolerated as the original, and is preferred by patients who want to stay home.
Outpatient ESHAP for recurrent lymphomas
Original IP ESHAP Modified OP ESHAP
Hospitalize 5-6 days Start in clinic
daily home nurse visits to manage pump
oral hydration, IV hydration + K in clinic
etoposide continuous OP one-hour infusion
infusion, day 1-4
methylprednisolone day 1-4 same
cisplatin continuous same, but with infusion pump
infusion, day 1-4
cytarabine 2-hourinfusioOP two-hour infusion
Paclitaxel as a three- vs. 24-hour infusion should have an answer from the ongoing trials. Unless a compelling survival advantage is shown by the 24-hour way, which seems highly unlikely, the cat will have been long out of the bag.
How much money will be saved by switching to outpatient?
It may be a lot. I pulled the bills on my patient who died of lymphoma progressed on CHOP, ESHAP, and a phase II trial of high-dose chemo supported with CD34+ selected cells. His ESHAP courses were expensive: generally about $10,000. Of this, about $3,500 was for the necessary chemotherapy, IVs, antiemetics, physician, and ancillary charges. He was charged nearly $500 a day for the inpatient bed, and lots of things happened that were suddenly out of my control. Labs got ordered STAT, tripling their cost; all sorts of lab tests got tacked on, such as RDWs and daily magnesiums, etc. Plus, inpatient charges for the same tests such as CBCs are more than double the outpatient. His 20% co-payment could have been as low at $700, compared to the nearly $2,000/cycle for inpatient therapy.
How do you "fix" the doctors in the examples above?
Stick with the facts, and appeal to competence first. Given the choice, reasonable doctors will change practice to the new technique. Case 1 should be straightforward. With paclitaxel, there is more than enough evidence to document safety of the three-hour infusions. Ask Dr. 24-hour why he/she gives it that way; it may be unfamiliarity with more recent regimens. Give him/her a written locally-approved plan for the three-hour infusion.
Case 2, management of a dying patient with non-small cell lung cancer is more difficult. (Good guidelines exist. See ASCO Non-small cell lung cancer expert panel. Clinical practice guidelines for the treatment of unresectable non-small cell lung cancer. J Clin Oncol 1997;15:2996-3018.) Failure to adopt new ways of doing things, to use new and superior regimens, and to treat with ineffective regimens as second- and third-line treatment, is not a crime. But add these traits to an unwillingness to use hospice, or even discuss when a patient is clearly dying, and you have several indicators of real trouble. Such care can hardly be expected to be optimal patient care, and is too wasteful of precious resources (like the last days of the patient).
Take home message
Most regimens can be given in the outpatient setting, even infusional ones. The cost savings may be considerable. In general, there is little evidence that IP or OP setting is superior for any regimen.