Phase I Cancer Trials

By Miller, Matthew | The Hastings Center Report, July 2000 | Go to article overview

Phase I Cancer Trials


Miller, Matthew, The Hastings Center Report


A Collusion of Misunderstanding

A dilemma confronts physician-investigators ... As physicians they are dedicated to caring for their patients ... As investigators they are dedicated to caring for their research ... These two commitments conflict whenever an individual physician-investigator comes face to face with an individual patient/subject.[1]

In 1995, having just finished a fellowship in medical oncology, I was installed for a three-month stint as acting clinical director of Phase I trials at the Dana-Farber Cancer Institute. The Dana-Farber is a cancer center characteristic of elite academic cancer centers that engage both in clinical research, including high-volume Phase I trials, and direct patient care. My duties included caring for all patients already enrolled in Phase I trials and inviting new patients to participate in ongoing and newly sanctioned trials.

Phase I trials lack control groups, and unlike Phase II and III trials they do not test hypotheses (such as whether new drug X is at least y percent effective in disease Z, or whether new drug X is better than old drug Y). Rather, they address an estimation problem: drugs that have demonstrated promising anticancer effects in animals are administered to terminally ill cancer patients in an attempt to estimate the highest dose human beings can tolerate. Evaluating a drug's anticancer effect in human cancers, a primary objective of subsequent phase II and III trials, is not a defined goal in Phase I studies.[2]

Having taken care of adults with terminal cancer before joining the Phase I team, I had witnessed the desperation that motivates many patients to participate in these trials and recognized in a vague but fateful way the peripheral regard most patients had for the sacrifices they were being asked to make on behalf of science, researchers, and future generations of patients. What I did not appreciate, prior to my direct involvement, was the moral difficulty inherent in navigating the tensions between patient care and research.

My experience taking care of, enrolling, and doing research on patients in Phase I cancer trials has forced me to question assumptions implicit in the actions I engaged in daily. Some of these assumptions reveal structural problems peculiar to Phase I trials, which in turn suggest design modifications that have moral consequences within these trials. Other assumptions underpin a more fundamental tension not amenable to technical solution, raising residual questions about human investigation generally, such as whether and under what conditions it is justifiable to trade on patients' hopes. (I should note that the difficulties I encountered would not, I believe, have been substantively different had my experience with Phase I trials taken place at any other academic teaching hospital.)

Subjects and Response Rate

In the United States, subjects in noncancer Phase I (dose-toxicity) studies are usually healthy volunteers. This choice is defended, by its proponents, on two grounds.[3] First, sick persons are vulnerable and should thus be protected from harm, and second, results from healthy persons are free from the distorting effect that disease can have on drug metabolism and tissue tolerance. Critics of this practice argue that even though the risk of injury to healthy subjects is very small, because there are no health-related benefits the balance of risk and benefit is unacceptable.[4] Others challenge this practice on scientific grounds, claiming that drug metabolism is so different in healthy from sick individuals that any transfer of results from healthy to sick may be dangerously misleading.[5] Because Phase I cancer trials use drugs that often produce their effects by causing damage to DNA, with attendant concerns about long-term carcinogenic consequences, subjects in Phase I cancer trials are never healthy volunteers.

To be considered for Phase I cancer trials patients must have exhausted all known therapeutic options and have a life expectancy of at least three to four months. …

The rest of this article is only available to active members of Questia

Already a member? Log in now.

Notes for this article

Add a new note
If you are trying to select text to create highlights or citations, remember that you must now click or tap on the first word, and then click or tap on the last word.
One moment ...
Default project is now your active project.
Project items

Items saved from this article

This article has been saved
Highlights (0)
Some of your highlights are legacy items.

Highlights saved before July 30, 2012 will not be displayed on their respective source pages.

You can easily re-create the highlights by opening the book page or article, selecting the text, and clicking “Highlight.”

Citations (0)
Some of your citations are legacy items.

Any citation created before July 30, 2012 will labeled as a “Cited page.” New citations will be saved as cited passages, pages or articles.

We also added the ability to view new citations from your projects or the book or article where you created them.

Notes (0)
Bookmarks (0)

You have no saved items from this article

Project items include:
  • Saved book/article
  • Highlights
  • Quotes/citations
  • Notes
  • Bookmarks
Notes
Cite this article

Cited article

Style
Citations are available only to our active members.
Buy instant access to cite pages or passages in MLA, APA and Chicago citation styles.

(Einhorn, 1992, p. 25)

(Einhorn 25)

1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

Cited article

Phase I Cancer Trials
Settings

Settings

Typeface
Text size Smaller Larger Reset View mode
Search within

Search within this article

Look up

Look up a word

  • Dictionary
  • Thesaurus
Please submit a word or phrase above.
Print this page

Print this page

Why can't I print more than one page at a time?

Help
Full screen

matching results for page

    Questia reader help

    How to highlight and cite specific passages

    1. Click or tap the first word you want to select.
    2. Click or tap the last word you want to select, and you’ll see everything in between get selected.
    3. You’ll then get a menu of options like creating a highlight or a citation from that passage of text.

    OK, got it!

    Cited passage

    Style
    Citations are available only to our active members.
    Buy instant access to cite pages or passages in MLA, APA and Chicago citation styles.

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn, 1992, p. 25).

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences." (Einhorn 25)

    "Portraying himself as an honest, ordinary person helped Lincoln identify with his audiences."1

    1. Lois J. Einhorn, Abraham Lincoln, the Orator: Penetrating the Lincoln Legend (Westport, CT: Greenwood Press, 1992), 25, http://www.questia.com/read/27419298.

    Cited passage

    Thanks for trying Questia!

    Please continue trying out our research tools, but please note, full functionality is available only to our active members.

    Your work will be lost once you leave this Web page.

    Buy instant access to save your work.

    Already a member? Log in now.

    Oops!

    An unknown error has occurred. Please click the button below to reload the page. If the problem persists, please try again in a little while.