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Chemotherapy Studies that Involve Taxol(Paclitaxel)
Covered here are
- Taxol
- Taxol and Epirubicin
- Taxol, carboplatin vs Mitoxantrone
- Strontium, Doxorubicin, ketoconazole, Paclitaxel, estramustine.
- Taxol, Vinorelbine (Pac-Vin)(2007 ASCO Annual
Meeting).
- Taxol, Emcyt, Carboplatin as a ≥ 2nd line
chemotherapy following failure of taxotere. See Table 6.
See also Chemotherapy
Studies that Involve Taxol(Paclitaxel) in various combinations
Another page to read is taxol with
high dose pulsed calcitriol. This page, except for Table 6 doesn't cover
2nd line studies.
Definitions
PR - partial response
Table 1. Taxol (Paclitaxel).
|
Ref |
Phase, Number of Patients |
Paclitaxel |
PSA Response Rate
>50%
Decline.
|
Median Duration of Response |
median survival |
|
(1) |
43, some prior
emcyt use. all metastatic. |
Paclitaxel 80mg/m2 over 1 hour. 6 weeks on and 2 weeks off. |
PSA > 50%
decline: 36.1%, 13 of 36 patients.
Objective
Response: 5 of 16 patients or 31.2%.
9 stable disease. |
PSA: 4.2 months.
|
Median survival 12.8 months |
|
(2) A Frassoldati et al 2001 |
9, chemo-naive except for 2 with previous emcyt. |
100 mg/m2 over 1 hour, 6 consecutive weeks followed by 2
weeks of rest. Dose reduced to 80mg/m2 for grade 2 peripheral
neuropathy. |
PSA Response Rate (≥ 50% decline in PSA was 75%. (a) |
No modification of radiological findings was observed.
|
Mean response duration was 5.3 months (range 3-8) &
one-year actuarial survival was 83%. |
|
(3) Cancer 2000. |
18 patients. All chemo-naive. All mHRPC. |
150mg/m2 over 1 hour for 6 of 8 weeks. |
7 of 18 (39%) patients had Response Rates (≥ 50%. (b) |
18 patients had measurable disease: 1 complete response
in the lung and 3 partial responses - 1 in liver, 2 in lymph nodes.
|
- |
(1)
Chiappino
I, Destefanis P, Addeo A, Galetto A, Cucchiarale G, Munoz F, Zitella A,
Ferrando U, Fontana D, Ricardi U, Tizzani A, Bertetto O., Activity of weekly
paclitaxel in advanced hormone-refractory prostate cancer, Am J Clin Oncol.
2007 Jun;30(3):234-8.
Toxicities noted are:
anemia grade 3, 16%; neutropenia grade 3-4, 12%) and moderate nonhematologic
toxicities (thrombosis/embolism 10%; fatigue all grades, 60%).
(2) Antonio Frassoldati, et al, Weekly
Paclitaxel in Hormone-Refractory Prostate Cancer(HRPC), ASCO Annual Meeting
2001, abstract # 2396.
(a) All but one patient had a PSA decline that
reached a nadir between 4th and 8th week. The mean relative PSA reduction
was 61%(range 19-96%). Pain improved in 6 of 7 patients who were previously
symptomatic and disappeared entirely in 4 patients. Peripheral neuropathy
occurred in all patients - grade 2 adverse p/n event occurred in 4 cases (4
of 9). No patient showed an absolute neutrophil count or platelet reduction
grade 1.
(3) Trivedi C, Redman B, Flaherty LE, Kucuk O,
Du W, Heilbrun LK, Hussain M., Weekly 1-hour infusion of paclitaxel.
Clinical feasibility and efficacy in patients with hormone-refractory
prostate carcinoma, Cancer. 2000 Jul 15;89(2):431-6. Erratum in: Cancer 2000
Sep 15;89(6):1412.
(b) Peripheral neuropathy was the major high
grade toxicity with 6 patients (35%) developing grade 3 toxicity.
Table 2. Paclitaxel and Epirubicin.
|
Ref |
Phase, Number of Patients |
Paclitaxel and epirubicin |
PSA Response Rate
>50%
Decline.
|
Median Response Rate |
Median time to progression or median survival |
|
(1) |
II, 32 |
Paclitaxel 70mg/m2 and epirubicin 30 mg/m2 every week for three months |
57%
|
- |
Median time to PSA progression 5.5 months; disease progression 7.6
months; survival 12.9 months |
(1)
Neri B, Cipriani G, Fulignati C, Turrini M,
Ponchietti R, Bartoletti R, Della Melina A, Di Cello V, Dominici A, Maleci
D, Raugei A, Villari D, Nicita G. Weekly paclitaxel and
epirubicin in the treatment of symptomatic hormone-refractory advanced
prostate carcinoma: report of a phase II trial. Anticancer Drugs. 2005
Jan;16(1):63-6.
Table 3. Paclitaxel, Carboplatin vs Mitoxantrone(Novantrone).
|
Ref |
Phase, Number of Patients |
Paclitaxel-Carboplatin |
Mitoxantrone |
PSA
Response Rate
>50% |
Median Response Rate |
Median time to progression or median survival |
|
|
(1)* |
II, 34 total (ongoing study) |
Paclitaxel 175 mg/m2 + carboplatin AUC 5 IV on day 1 of every 3 week
cycle |
|
44% 4 of 9 analyzed patients |
|
|
|
|
(1) |
same as above |
|
12 mg/m2 on day 1 of 3 week cycle |
8.3% 1 of 12 analyzed patients |
|
|
|
(1) Cabrespine, L. Guy,
P. Chollet, J. Fleury, F. Gachon, H. Curé, M. Mouret-Reynier, I. Van Praagh,
F. Penault-Llorca, J. Bay Phase II study of paclitaxel carboplatin
combination versus mitoxantrone in patients with hormone-refractory prostate
cancer. Presented at the 2005 Prostate Cancer Symposium, American Society
for Clinical Oncology, 2005.
*Study is
ongoing. Quality of life is not different between the two arms.
Patients
presented higher level of ChroA at includsion have a higher decline
of PSA.
Table 4.
Strontium, Doxorubicin, ketoconazole, Paclitaxel, estramustine.
|
Ref
|
Phase, Number of Patients |
Strontium-89 (S)
doxorubicin (D), ketoconazole (K),
Paclitaxel(P),
estramutine(E) |
PSA
Response Rate
>50% |
Median Response Rate |
Median time to
progression or median survival |
|
(1)* |
None,25 |
S 4 mCi on wk 1 day 1, wks 1,3,5 D 20 mg/m2 first day each wk with K 400
mg 3 times a day for 7 days. Wks 2,4,6 P 100 mg/m2 with E 280 mg orally
3 times a day for 7 days. Responders received 4 8 wk. courses, then
maintenance daily K. |
18 of 20 patients evaluated so far |
- |
Progression free survival range from 2 to 25 months |
(1) H. Henary,
R. J. Amato Bone-Targeted Therapy for Androgen-Independent Prostate Cancer (AIPCa)
Presented at the 2005 Prostate Cancer Symposium, American Society of
Clinical Oncology, 2005. *Enrollment is ongoing.
Table 5.
Paclitaxel (Taxol) and Vinorelbine (Pac-Vin)
|
Ref
|
Phase, Number of Patients |
Paclitaxel |
Vinorelbine |
PSA
Response Rate
>50% |
Measurable
Disease Response Rate |
Median time to
progression or median survival |
|
Sewak et al(1)@, * |
30, II
|
40 mg/m2 (1 hr); days 1 and 8 of 21-day cycle. |
20 mg/m2 I-V; days 1 and 8 of 21-day cycle. |
20% PSA RR, with 63% achieving Stable Disease |
10 patients had measurable disease. PR was 20%; 70% had stable disease. |
Median overall survival was 9.7 months. Median progression free survival
was 5.1 months. |
(1)
S.
Sewak, S. Kosmider, V. Ganju, A. Woollett, B. Le, E. Yeo, M. Henry, R. Bell,
A phase II study of paclitaxel and vinorelbine (Pac-Vin) in
hormone-refractory metastatic prostate cancer (HRPC): A final update,
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I.
Vol 25, No. 18S (June 20 Supplement), 2007: 15505. Note that pre-clinical
models had shown synergy between paclitaxel and vinorelbine.
@Previous radiotherapy, strontium therapy, 1 line of chemotherapy (17% had 1
prior chemotherapy), and concurrent bisphosphonate therapy were allowed.
*Grade 3&4 toxicities were: neutropenia 8%, febrile neutropenia 4%,
infection 2%, anemia 3%, lethargy 1%, and somnolescence 1%. 1 pt died as a
result of neutropenic sepsis.
Table 6. Taxol, Emcyt, Carboplatin as a ≥ 2nd line
chemotherapy following failure of taxotere.
This is 1 study TEC as a 2nd line chemotherapy. There
might be others that will be added later.
| Reference |
Phase and No. of Patients |
Taxol (a) |
Emcyt |
Carboplatin (b) |
PSA RR(≥50% decline in PSA |
Measurable Disease RR |
Median time to progression or median survival |
| (1) Sella A, Oncology 2009 |
Pilot study. 15 patients. |
80mg/m2 weekly with dexamethasone and cimetidine premedication. |
140mg on days -1, 0 and +1 every week. |
AUC 6 day 1 of a 21 day cycle. |
9 pts
(60%), with another 3
pts(20%) with PSA stable disease. |
Partial response in 6 pts (40%) |
Median duration of progression-free survival was 4.0 months
(range 1.1-13 mos). Median survival was 14.6 mos. |
(a) I could find no weeks off for this study (e.g., 3 of 4 weeks, 6 of 8
weeks or every other week) so perhaps patients were treated continuously.
(b) A lower dose of carboplatin might provide a protocol with less toxicity.
A dose sometimes used for carboplatin is AUC 2-3 or 200mg on a weekly basis
(same weeks as Taxol).
(1) Sella A, Yarom N, Zisman A, Kovel S., Paclitaxel,
estramustine and carboplatin combination chemotherapy after initial
docetaxel-based chemotherapy in castration-resistant prostate cancer.,
Oncology. 2009;76(6):442-6. Epub 2009 May 5. Department of Oncology, Assaf
Harofeh Medical Center, Zerifin, Israel.
a_sella@asaf.health.gov.il
Toxicity: fatigue grade 1–2 in 5 (33%) and grade 3 in 2 PTS (13%),
neuropathy
grade 2 and grade 4 in 1 patient each (7%), as well as single episodes of
edema (grade 3), diarrhea (grade 2),vomiting (grade 1) and rash (grade 2).
Myelosuppression
was mild. 1 patient developed neutropenic fever. One patient died due to
brain hemorrhage with prolonged thrombocytopenia, and an additional patient
died due to respiratory failure unrelated to the therapy. The latter patient
progressed after the first cycle and developed pneumonia 3 weeks after
complete recovery of blood counts. Overall, 4 PTS (27%)
withdrew from therapy due to toxicity: 2 PTS with neurotoxicity, a single
patient with prolonged thrombocytopenia (that led to the brain hemorrhage)
and a single patient with neutropenic fever.
TEC was toxic in patients who had previously received
taxotere with approximately one-third of the patients withdrawing from
therapy.
Another page with taxol information is
taxol with
high dose pulsed calcitriol for other doses, schedules of first line
TEC.
Author: Barb Minton, 3/16/2005; Updated 18 January 2010, H. Hansen
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