Re: [MOL]Suzanne [02726] Medicine On Line

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Re: [MOL]Suzanne

Boy Suzanne, thats a heavy load I just read about and was very sorry to
hear what you are going through.  I don't know if this will help; but I am
on a breathing machine (they first thought oxygen around the clock); bu the
breathing machine has helped me to a great extent and I only use it at
nights.  I even know some people who have been able to go off the breathing
machine; so thats hopeful new's!  I realized that you do not have ovarian
cancer; but the information on the drug is useful and therefore why I am
sending it to you.  I have been all over the web to try and get information
on atopocide and connot find a thing on it.  Your friend, lillian

Ovarian cancer is the sixth most common cancer worldwide; it carries the
highest mortality of all gynecologic malignancies. Extensive research over
the last two decades has led to the development of a number of cytotoxic
drugs with high response rates, but responses are usually short-lived and
only 30% of women are alive five years after diagnosis. Ovarian cancer is
usually epithelial in origin; only 10 to 15% of tumors are of germ cell or
stromal origin. Risks increase with older age at first birth, early
menarche, and late menopause. Risks are reduced by successful pregnancies,
prolonged breast feeding, and use of birth control pills (the longer the
use, the greater the protection). 

One reason for the poor prognosis is the absence of pronounced symptoms
early in the course of disease. In two thirds of patients, the disease has
spread beyond the pelvis by the time the cancer is detected. Treatment
requires careful surgical debulking followed by platinum-based
chemotherapy. The addition of paclitaxel (Taxol/Bristol-Myers Squibb)
improves the prognosis. Other drugs in trial for advanced ovarian cancer
include docetaxel (Taxotere/Rhone-Poulenc Rorer), gemcitabine, and the
camptothecins. Recently, the Food and Drug Administration (FDA) approved
the camptothecin topotecan (Hycamtin/SmithKline Beecham) for the treatment
of patients with refractory metastatic ovarian carcinoma. (The FDA has also
approved gemcitabine and the camptothecin irinotecan, but for other types
of cancer; see see Gemcitabine Approved for Pancreatic Cancer and
Irinotecan Approved for Advanced Colorectal Cancer.) Topotecan acts by
inhibiting the enzyme topoisomerase I, which is necessary for maintaining
proper DNA structure during cell division. Topoisomerase inhibition results
in DNA chain breakage during replication, causing death of dividing cells.
Studies have shown that about 15% of patients with refractory ovarian
cancer respond to topotecan. (Similar response rates have been reported for

Topotecan is given in a dose of 1.5 mg/m2 IV for 30 minutes daily over 5
days during a 21-day course of therapy. At least four courses are
recommended because median time to response is approximately 9 to 12 weeks.
Adverse effects are common, but usually tolerable. In clinical trials,
three quarters of patients had nausea, about half had vomiting, and a third
or more had fatigue, diarrhea, abdominal pain, constipation, and fever.
Alopecia occurred in about half of patients, and most had complete
alopecia. The dose-limiting toxicity was myelosuppression, in particular
neutropenia and thrombocytopenia. Severe neutropenia (grade 4, In one
clinical trial comparing topotecan with paclitaxel in 226 women with
recurrent cisplatin-resistant ovarian cancer, topotecan was administered as
a 30-minute infusion of 1.5 mg/m2/day for five days, and paclitaxel as a
3-hour infusion of 175 mg/m2/day. Both drugs were given in 21-day cycles.
The objective response rates were about 20% with topotecan and 13% with
paclitaxel. Median duration of response was 32.1 weeks for topotecan and
19.7 weeks for paclitaxel, and median survival was 61.3 weeks for topotecan
and 42.6 weeks for paclitaxel. Neutropenia was more frequent in topotecan
patients (80% had grade 4 neutropenia compared with about 20% of paclitaxel
patients). Anemia and thrombocytopenia were also more common in the
topotecan group. Sepsis occurred in 5.5% of topotecan patients versus 1.3%
of paclitaxel patients. 

Currently, there is a 400-patient trial under way of topotecan in
combination with cisplatin as first-line treatment for ovarian cancer. In
addition, topotecan is under investigation for recurrent small-cell cancer,
breast cancer, leukemia, pediatric tumors, and lymphoma. Also under
investigation is an oral capsule formulation. (Lorigan PC, et al. Drugs.
1996;51:571-584. Additional information is available from the


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