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A scientific article
There have been a number of clinical studies that have tested cancer vaccines.
Thus far, there is only one cancer vaccine found to improve overall survival.
Sipuleucel-T (Provenge®) is approved for use in some men with metastatic
prostate cancer. It stimulates an immune response to prostatic acid phosphatase
(PAP), an antigen present on most prostate cancers. In a clinical trial, Provenge
increased the survival of men with hormone refractory metastatic prostate cancer
by about 4 months. The vaccine is customized for each patient. Using
leukopheresis, the patient's APCs are harvested and then cultured with a protein
called PAP-GM-CSF. This protein consists of PAP linked to another protein called
granulocyte-macrophage colony-stimulating factor (GM-CSF). GM-CSF
stimulates the immune system and enhances antigen presentation. APC cells
cultured with PAP-GM-CSF are then infused into the patient with three treatments,
usually two weeks apart. The exact mechanism of action of sipuleucel-T is
unknown but, it is likely that the APCs that have taken up PAP-GM-CSF stimulate
T cells to kill tumor cells that express PAP. Common side effects included fever,
chills, fatigue, back and joint pain, nausea, and headache. These most often started
during the cell infusions and resolved within one to two days.
Even the studies of vaccines that did ultimately not work have taught us important
lessons:
1. Cancer vaccines are well-tolerated.
A number of Phase I and II trials have shown that cancer vaccines are generally
well-tolerated, particularly with the viral and peptide vaccines. Phase I trials have
reported very few significant toxicities with these vaccines. The most common
toxicity in all of these trials has been local irritation at the site of the injection. In
fact, it appears that patients that have a stronger local reaction to the injection may
have a better response of the tumor to the treatment. This may be because a local
reaction serves as a marker for people who have a good immune response to the
vaccine. Patients with strong local reactions will likely have a strong reaction to
the tumor as well.
2. Cancer vaccines induce an immune response.
In both Phase I and Phase II trials, levels of immune activity have been measured
in patients receiving cancer vaccines. Routinely, objective measures have shown
an increase in the immune activity in a number of patients receiving cancer
vaccines. In addition, patients who have a good immune response by objective
measures have a better response of their tumors to the vaccine.
3. Several cancer vaccines show a good tumor response compared to historical
results.
Recently, the results of a non-randomized trial utilizing a melanoma vaccine were
reported. Patients receiving the vaccine had a 5-year overall survival of 44%.
Given the advanced disease in these patients, these results were quite good, and
noticeably higher than historical surgical series of patients with similarly advanced
disease showing 5-year overall survival rates of 20-25%. Another promising trial
was recently reported which used a prostate cancer vaccine in patients with
progressive disease (judged by rising PSA levels) after local therapy for prostate
cancer. After a year and a half, 45% of patients did not have further increases in
their PSA.
4. Results of Phase III, randomized trials have been disappointing.
Despite the promising results in earlier trials, several large randomized trials have
failed to show an overall survival advantage with the use of vaccines. A large trial
by the Southwest Oncology Group for patients with melanoma who did not have
spread of their disease to the lymph nodes showed no improvement in overall
survival for patients who received the vaccine following surgery compared to
patients who underwent surgery alone. Another trial for patients with renal cell
carcinoma showed a small decrease in the percentage of patients who had
progression of their cancer with the addition of a cancer vaccine.
A story
Inspection, palpation, percussion, auscultation – the unalterable, ever-applicable
tetrad. Whatever part of the patient you examine, whatever disease you suspect, the
four actions must be done in that order. You look first, then feel; when you have
felt, you may tap, but not before – and last of all comes the stethoscope.
I began to learn how to look at a patient so that even looking at his fingernails I
could make a dozen diagnoses. They taught us to feel lumps, livers and spleens;
how to percuss correctly and to understand the evasive murmurs transmitted
through a stethoscope.
Dr. Maxworth took his firm round the ward every Wednesday morning. He was
a thin little man who always appeared in public in black coat and striped trousers.
He was not really interested in students. For most of the round he forgot we were
with him, but would suddenly recall our presence by throwing some instruction
over his shoulder. He was a specialist in neurology, the diseases of the nervous
system. As almost all the nervous diseases we saw in the ward appeared to be fatal,
it seemed to me a very depressing speciality. But Maxworth drew certain pleasure
from it. He was not concerned with treating his patients and making them better,
but was delighted if he managed to make a diagnosis before the proof of the
postmortem examination. He was, his assistant said, a typical physician.
I began to see how the ward was managed by Sister, whom I avoided like a pile
of radium. Every bodily function that could be measured – the pulse, the amount of
urine, the quantity of vomit, the number of baths – was carefully recorded against a
patient’s name in the treatment book, which reduced the twenty humans in the
ward to a daily row of figures in her aggressive handwriting.
There were two functions of the physiology in which Sister took special
interest. One was temperature. The temperature charts shone neatly from the foot
of the beds, and each showed a precise horizontal zigzag of different amplitude.
The temperatures were taken by the junior nurses, who used four or five
thermometers. However, the figures were looked as insignificant, because Sister
substituted figures of her own, if the ones of the patient did not fit with her notion
of what the temperature of the case ought to be.
The other particular concern of the Sister was the patient’s bowels. A nurse was
sent round the ward every evening with a special book to ask how many times each
inmate had performed during the past twenty-four hours. The number of occasions
was written in a separate square at the foot of the temperature chart. A nought was
regarded by Sister as unpleasant, and more than two blank days she took as a
personal insult. Treatment was simple. One nought was allowed to pass without
punishment, but two automatically meant purgative, three – castor oil, and four –
the supreme penalty of enema.
We rapidly became accustomed to our position of inferiority to everyone on the
ward staff. We did all the medical chores: urine testing, gruel meals in patients
with duodenal ulcers, blood samples and a few simple investigations. For the first
few weeks everything seemed easy. It was only at the end of the three-month’s
practice that I realized how ignorant I was.
A poem
Escaping from drugs!
Take me away; take me far
Where I cannot listen to anyone
Where there isn’t an alcohol bar
Take me somewhere where there is no speed
Where drugs do not exist
Somewhere where I can’t take any weed
Take me somewhere that I can call home
Don’t leave me here in the middle of the street
I need your help I can’t do this alone!
Take me somewhere safe; just take me away
Don’t leave me suffering, just set me free
Give me the path to freedom and I’ll find the way!