|
Chemotherapy Updates for
Studies that Involved Taxotere(Docetaxel)
Newest update was done 20
Dec. 2007.
Table 1. Docetaxel and Estramustine Phosphate (Emcyt).
|
Ref |
Phase, Number of Patients |
Docetaxel |
Emcyt |
Prednisone |
PSA
Response Rate
>50%
|
Median Response Rate |
Median time to progression or median survival |
|
(1) |
None,
39 |
70 mg /m2 on day 2 of 21 day cycle for four cycles; if no progression,
then two more cycles |
280 mg 3 times daily on days 1-5 and 7-11 |
10 mg once daily |
At 11 month followup
48% |
Not reported |
Not reported |
|
(2)* |
I, 11 |
3 patients, 30 mg/m2; 3 patients, 35mg/m2; 3 patients, 40 mg/m2; 2
patients 45 mg/m2. all weekly |
840 mg per day |
None |
9 after 2
cycles of therapy |
Not reported |
Not reported |
|
(3)* |
II,62 |
70 mg/m2 day 2, every 3 weeks |
280 mg 3 times daily, 1 day before docetaxel for 5 days |
None |
38 (61.3%)
|
Not reported |
Time to progression 14 months; median survival 24 months |
|
(4) |
None, 34 |
- |
560 mg per day |
- |
24% |
- |
Median duration of response 8 months; 2 year survival rate of responders
was 83% and 44% in non-responders |
|
(5) |
None, 9 Japanese |
55 mg/m2 every 3 weeks with LHRH and daily oral dexamethasone |
- |
- |
75% |
- |
Time to progression 7.9 months, median survival 8.5 months |
(1)
Beohmer A,
Anastasiadis AG, Feyerabend S, Nagele U, Kuczyk M, Schilling D, Corvin
Merseburger AS, Stenzl A; Docetaxel, estramustine and prednisone for
hormone-refractory prostate cancer: a single-center experience. Anticancer
Res. 2005 Nov-Dec;25(6C):4481-6.
(2)
Coccaro M, Tartarone A,
Romano G, Ardito R, Di Renzo N. Dose-finding study of weekly docetaxel plus
estramustine in patients with hormone-refractory metastatic prostate cancer.
Tumor. 2005 Jul-Aug;91(4):314-6.
*The authors state that docetaxel 35/m2 had good
tolerability with
estramustine
(3)
Nelius T,
Reiher F, Lindenmeir T, Klatte T, Rau O, Burandt J, Filleur S, Allhoff
EP. Characterization of prognostic factors and efficacy in
a phase-II study with
docetaxel and estramustine for advanced hormone refractory
prostate cancer.
Onkologie. 2005 Nov;28(11):573-8.
*The authors state there was a survival advantage for
patients with early chemotherapeutic intervention.
(4)
Hirano D,
Minei S, Kishimoto Y, Yamaguchi K, Hachiya T, Yoshida T, Yoshikawa T, Endoh
M, Yamanaka Y, Yamamoto T, Satoh Y, Ishida H, Okada K, Takimoto Y.
Prospective study of estramustine phosphate for hormone refractory prostate
cancer patients following androgen deprivation therapy. Urol
Int.2005;75(1):43-49.
(5)
Miyoshi Y,
Uemura H, Nakamura M, Hasumi H, Sugiura S, Makiyama K,
Nakaigawa N, Kishida T, Ogawa T, Yao M, Kubota Y.
Treatment of androgen-
independent, hormone-refractory prostate cancer with
docetaxel in Japanese
patients. Int J Clin Oncol. 2005 Jun;10(3):182-6.
Table 2. Docetaxel,
Emcyt, and Suramin
|
Ref |
Phase, Number of Patients |
Docetaxel |
Emcyt |
Suramin |
PSA
Response Rate
>50%
|
Median Response Rate |
Median time to progression or median survival |
|
(1) |
none, 42, HRPC, symptomatic, chemo-naive. |
70 mg/m2 day 2 every 28 days |
10mg/kg orally daily on days 1 to 21 every 28 days |
2150 mg every cycle (median of 8.8 cycles) |
100% (>90% in 76.2% of pts.) |
|
Time to progression 57 weeks; median survival 132 weeks |
(1) Safarinejad MR.
Combination chemotherapy with docetaxel, estramustine and
suramin for hormone refractory prostate cancer. Urol
Oncol. 2005 Mar-
Apr;23(2):93-101.
Table 3. Docetaxel, Liposomal doxorubicin (doxil).
|
Ref |
Phase, Number of Patients |
Docetaxel |
Liposomal doxorubicin
(PEG-LD)
|
PSA
Response Rate
≥50%
|
Median Response Rate |
Median time to progression or median survival |
|
(1)* |
I,48 of which 27 were HRPC.
11 patients had
at least 1 prior chemo. |
Escalating dose starting at 20mg/m2 per week for three out of four weeks |
Escalating dose starting at 6mg/m2 per week for three out of four weeks |
PSA RR was 50%
(12 of 24) and the objective RR was 16% (3 of 19.) |
Not reported |
Not reported |
|
(2)* |
II, 14 |
- |
50 mg/m2 (first dose was randomized with half pts. receiving doxorubicin
and half liposomal doxorubicin |
14% |
- |
- |
(1)
Kouroussis
Ch, Androulakis N, Vamvakas L, Kalykaki A, Spiridonakou S, Kentepozidis N,
Saridaki Z, Xiropoulou E, Georgoulias V. Phase I study of weekly docetaxel
and liposomal doxorubicin in patients with advanced solid tumors. Oncology.
2005;69(3):202-7. Epub 2005 Aug 26.
*Maximum tolerated doses were 35mg/m2 per week for
docetaxel and 14
mg/m2 per week of PEG-LD.
(2)
Harris KA, Harne E, Small
EJ. Liposomal doxorubicin for the treatment of
hormone-refractory
prostate cancer. Clin Prostate Cancer. 2002 Jun;1(1):37-41.
*Note that this study was done in 2002, but does provide
a comparison to the
previous study.
Table 4. Docetaxel,
Zoledronic Acid (Zometa).
|
Ref |
Phase, Number of Patients |
Docetaxel |
Zoledronic Acid |
PSA
Response Rate
>50%
|
Median Response Rate |
Median time to progression or median survival |
|
(1) |
None, 25 |
30 mg/m2; premedication with
dexamethasone |
4 mg i.v. every four weeks |
48% (58% receiving this as a first-line therapy) |
Not reported |
7 months to progression; 16 months survival |
(1)Bertelli G, Heouaine
A, Arena G, Botto A, Garrone O, Colantonio I, Occelli M, Fea E,
Biubergia S, Merlano M.
Weekly docetaxel and zoledronic acid every 4 weeks in hormone
refractory prostate
cancer patients. Cancer Chemother Pharmacol. 2006 Jan;57(1):46-51.
Epub 2005 Nov 5.
Table 5. Docetaxel,
Vinorelbine (Navelbine), Filgrastim (G-CSF).
|
Ref |
Phase, Number of Patients |
Docetaxel |
Vinorelbine |
Filgrastim |
PSA
Response Rate
>50%
|
Median Response Rate |
Median time to progression or median survival |
|
(1) |
II, 41 (19 with no prior chemo, 21 with at least one prior chemo) |
60 mg/m2 day 1 of 28 day cycle; dexamethasone 8 mg twice daily for 4
days starting 1 day prior to docetaxel |
15 mg/m2 days 1 and 8 of 21 day cycle |
After first 3 patients, days 2-6 and 9-13 |
37% with no prior chemo; 29% with prior chemo maintained for at least 4
weeks |
Not reported |
Not reported |
(1)
Goodin, S,
Rao KV, Kane M, Dave N, Capanna T, Doyle-Lindrud S, Engle E, Jin L, Todd M,
DiPaola RS. A phase II trial of docetaxel and vinorelbine in patients with
hormone-refractory prostate cancer. Cancer Chemother Pharmacol. 2005
Aug;56(2):199-204. Epub 2005 Apr 19.
Table
6. Docetaxel, Oblimersen sodium
|
Ref |
Phase, Number of Patients |
Docetaxel |
Oblimersen sodium |
PSA
Response Rate
>50%
|
Median Response Rate |
Median time to progression or median survival |
|
(1) |
II,28 |
75 mg/m2 on day 6 every three weeks |
7mg/kg/d days 1 through 8 every three weeks |
52% |
|
Median survival 19.8 months |
|
(2) |
57 Arm A; 58 Arm B
Chemo-naive
(emcyt exception) |
Arm A: 75,g,2 pm
day 5, q3 weeks. |
Arm A: 7mg/kg
days 1-7, q3 weeks. |
Not in abstract |
|
Not in abstract |
|
Arm B: 75mg/m2
q3 weeks. |
Arm B: None |
Oblimersen sodium is manufactured by Genta and has a brand name of Genasensa.
Their website provides this information:
Genasense
inhibits production of Bcl-2, a protein made by cancer cells that is thought
to block chemotherapy-induced apoptosis (programmed cell death). By
reducing the amount of Bcl-2 in cancer cells, Genasense may enhance the
effectiveness of current anticancer treatment. Genta is pursuing a broad
clinical development program with Genasense evaluating its potential to
treat various forms of cancer.
(1)
Tolcher AW, Chi K, Kuhn
J, Gleave M, Patnaik A, Takimoto C, Schwartz G, Thompson I, Berg K,
D’Aloisio S, Murray N, Frankel SR, Izbicka E, Rowinsky E. A phase II,
pharmacokinetic, and biological correlative study of oblimersen sodium and
docetaxel in patients with hormone-refractory prostate cancer. Clin Cancer
Res. 2005 May 15;11(10):3854-61.
(2)
Sternberg CN, et al, Multicenter, Randomized, EORTC trial 30021 of docetaxel
+ oblimsersen and docetaxel in patients with hormone refractory prostate
cancer, Abstract # 144, ASCO 2007 Prostate Cancer Symposium (February 2007.)
Video and Slides are on the ASCO website.
Table 7. Docetaxel and
Exisulind.
|
Ref |
Phase, No of patients |
Exisulind |
Docetaxel |
PSA decline >50% |
Median time to progression or survival |
|
(1)* |
I/II; 34 |
Oral twice daily for 21 day cycles; 150 or 250 mg. |
60 or 75 mg/m2 |
38% |
Median overall survival 16 months; median progression free 4.7 |
(1)Ryan, CW, Stadler WM,
Vogelzang NJ. A phase I/II dose-escalation study of
exisulind and docetaxel
in patients with hormone-refractory prostate cancer.
BJU Int. 2005
May;95(7):963-968.
*Response rates do not
suggest an improvement over single-agent docetaxel in
this population.
Recommended phase II dose was exisulind 250 mg and
docetaxel 60 mg/m2.
Table 8. Docetaxel, Emcyt,
Prednisone vs Mitoxantrone/prednisone
|
Ref |
Phase, Number of Patients |
Docetaxel, emcyt, prednisone |
Mitoxantrone, prednisone |
PSA Response Rate >50% |
Median Response Rate |
Median time to progression or median survival |
|
(1) |
II, 130 (randomly assigned to 3 treatment groups |
70 mg/m2 on day 2 of 21 day cycle, emcyt 280 mg p.o. tid on days 1
through 5 and 8 through 12, prednisone 10 mg daily |
- |
67% |
- |
Time to pregression 8.8 months; overall survival 18.6 months |
|
(1) |
- |
35 mg/m2 on days 2 and 9 of 21 day cycle, emcyt 280 mg p.o. tid on days
1 through 5 and 8 through 12, prednisone 10 mg daily |
- |
63% |
- |
Time to progression 9.3 months; overall survival 18.4 months |
|
|
- |
- |
12 mg/m2 every 3 weeks; prednisone 10 mg daily |
18% |
- |
Time to progression 1.7 months; overall survival 13.4 months |
(1)
Oudard S, Banu E, Beuzeboc P, Voog E, Dourthe
LM, Hardy-Bessard AC, Linassier C, Scotte F, Banu A, Coscas Y, Guinet F,
Poupon MF, Andrieu JM. Multicenter randomized phase II study of two schedules of docetaxel,
estramustine, and prednisone versus mitoxantrone plus prednisone in patients
with metastatic hormone-refractory prostate cancer. J Clin Oncol. 2005 May
20;23(15):3343-51. Epub 2005 Feb 28.
Table
9. Docetaxel plus Cisplatin
|
Ref |
Phase, Number of Patients |
Docetaxel, cisplatin |
PSA
Response Rate
>50%
|
Median Response Rate |
Median time to progression or median survival |
|
(1) |
None, 13 |
Docetaxel 30 mg/m2 weekly for 3 weeks; cisplatin 70 mg/m2 on day 1 (2
cycles were given) |
77% |
|
Median time to progression 3 months |
(1)Fujinami
K, Miura T, Takizawa A, Osada Y. [Combination chemotherapy with
docetaxel
and cisplatin in patients
with hormone-refractory prostate cancer]
Hinyokika Kiyo. 2005
Jan;51(1):5-8. Japanese.
Table 10. Docetaxel vs
Docetaxel plus thalidomide.
|
Ref |
Phase, Number of Patients |
Docetaxel |
Docetaxel and thalidomide |
Docetaxel, thalidomide, Avastin (bevacizumab) |
PSA
Response Rate
>50%
decline.
|
Measureable disease RR |
Median time to progression or median survival |
|
(1)* |
Follow-up analysis of Phase II, 73 total (48 received D + T, 25 received
D alone) |
30 mg/m2 weekly for 3 of 4 weeks |
- |
|
- |
- |
Median survival 14.7 months |
|
(1) |
Same |
- |
Docetaxel 30 mg/m2 weekly for 3 of 4 weeks; thalidomide 200 mg daily |
|
- |
- |
Median survival 25.9 months |
|
YM Ning, et al, ASCO 2007, abstract # 5114 (2) |
Phase II, chemo-naive, 39 pts. |
- |
- |
Docetaxel 75mg/m2; Bv 15mg/m2 both q3 wks. Thalidomide: 200mg qhs,
prednisone 10mg qd. |
34 pts (87%) had ≥ 50% PSA decline.
3 other pts had approx. 40% decline and 2 were stable.
|
17 pts. CR+PR+SD = 59% ORR. |
|
(1) S. Retter, Y.
Ando, D. K. Price, J. L. Gulley, P. M. Arlen, S. M. Steinberg, C.
Parker, W. L. Dahut, W. D. Figg, Follow-up analysis of a randomized phase II study of docetaxel (D) and thalidomide (T) in androgen-independent prostate cancer (AIPC):
Updated survival data and stratification by CYP2C19 mutation status. Paper
presented at the 2005 Prostate Cancer Symposium, ASCO, 2005.
*When survival
data was stratified by CYP2C19 status, there was no significant
difference in
survival. However, in patients who received only docetaxel,
those with
W2C19 had a suggestion of a trend towards improved survival.
(2) YM Ning, et al,
A Phase II trial of thalidomide, bevacizumab, and docetaxel in patients
(pts) with metastatic androgen-independent
prostate cancer (AIPC), ASCO Annual Meeting 2007, abstract
# 5114. Enoxaparin used for thrombosis prevention and pegilgrastim was used
if neutropenia > grade 3.
Significant toxicites were febrile neutropenia
(5/39); syncope (4/39); colon performation or fistula (2/39); grade 3
bleeding (2/39); thrombosis (2/39).
Table
11. Docetaxel and Mitoxantrone every 3 weeks.
|
Ref |
Phase, Number of
Patients |
Docetaxel and
mitoxantrone |
PSA
Response Rate >50%
decline |
Median Response Rate |
Median time to
progression or median survival |
|
(1) |
II, 97 |
60 mg/m2 and 8 mg/m2 respectively every 3 weeks for 6 cycles |
71%
|
- |
Median time to progression 14.4 months; mean survival 17.6 months |
(1)Heidenreich, C. H. Ohlmann, U. H. Engelmann Docetaxel (DOC) and
Mitoxantrone
(MIT) in the management of hormone refractory prostate cancer (HRPCA).
Presented at the 2005 Prostate Cancer Symposium, ASCO, 2005.
Table 12. Docetaxel
and DES.
|
Ref |
Phase, Number of Patients |
Docetaxel and DES (diethylstilbestrol) |
PSA
Response Rate
>50%
decline.
|
Measurable
Disease RR |
Median time to progression or median survival |
(1)* and (2)
|
II,29;
51% soft tissue mets and 93% bone mets.
|
DES 5 mg po the day prior to docetaxel and 1 mg po qd continuously in
combination with docetaxel 36mg/m2 for 3 weeks of a 4 week cycle.
Anticoagulated.
|
69%
(20 patients)
|
15 patients with measurable disease, 6 (40%,) had a partial
response.
|
Median time to progression was 6 months (range, 3-19 months).
|
po = by mouth; qd = every day.
(1) B. Montgomery, D. Lin, C. Ryan, M. Garzotto, T. M. Beer
Diethylstilbestrol and
docetaxel; a phase II study in patients with metastatic, androgen
independent prostate cancer.
Abstract from ASCO, 2005 Prostate Cancer Symposium. Reference (2) is the
publication of this study in Cancer.
*The authors comment that the combination of DES and docetaxel is very well
tolerated and toxicity is indistinguishable from docetaxel alone.
(2)
Montgomery RB, Nelson PS, Lin D, Ryan CW, Garzotto M, Beer TM.,
Diethylstilbestrol and docetaxel: a phase II study of tubulin active agents
in patients with metastatic, androgen-independent prostate cancer, Cancer.
2007 Jul 18; [Epub ahead of print].
The
addition of diethylstilbestrol to docetaxel modified tubulin composition and
improved the response of prostate cancer to chemotherapy in preclinical
models.
Toxicity:
Fifteen
patients (51%) suffered grade 3/4 toxicity. Two patients died of causes
unrelated to therapy and another died from a steroid-induced ulcer. Six
patients developed thrombosis and of those tested 75% had Factor V
mutations. The level of anti-coagulation was not indicated in the
abstract.
Table 13. Docetaxel
and vinblastine every 3 weeks.
|
Ref |
Phase, Number of Patients |
Docetaxel and vinblastine |
PSA
Response Rate
>50%
|
Median Response Rate |
Median time to progression or median survival |
(1)*
|
I/II, 20
|
Docetaxel 3 weekly doses at 20, 25, 30, 35, or 40 mg/m2; vinblastine 3
mg/m2
|
65%
|
-
|
Median time to progression 50 weeks
|
(1) W. J.
Tester, J. R. Ackler Phase I/II study of weekly docetaxel and vinblastine in
the treatment of hormone-refractory prostate cancer (HRPC).
Presented at the 2005 Prostate Cancer Symposium of the American
Society of Clnical Oncology, 2005.
*The MTD of docetaxel was 30 mg/m2.
Table 14. Docetaxel and
Capecitabine (Xeloda).
|
Ref |
Phase, Number of Patients |
Docetaxel and capecitabine(a) |
PSA
Response Rate
>50%
|
Median Response Rate |
Median time to progression or median survival |
(1)
|
II, 77
|
Docetaxel 60 mg/m2 every 21 days; capecitabine 1000 mg/m2 BID days 1-14
each 21 day cycle; maximum of 8 cycles
|
36%
|
|
Median progression free survival 5.1 months; estimated one year survival
71%.
|
(a)Capecitabine (Xeloda) is an orally administered fluoropyrimidine that is
metabolized to 5-fluorouacil (5-FU) by a series of enzymatic steps.
This takes place more readily within the tumor, where the concentration and
activity of the final activating enzyme is higher. The main side
effects are hand-foot syndrome, diarrhea and melosuppression.
(1)M. A. Kolodziej, M. A. Neubauer, R. E. Pluenneke, S. R. Rousey, M. A.
O'Rourke, S. Mull, K. A. Boehm, D. Ilegbodu, L. Asmar Results of a Phase II
trial of capecitabine and docetaxel in hormone-refractory prostate cancer.
Presented at the 2005 Prostate Cancer Symposium of the American Society for
Clinical Oncology, 2005.
Table
15. Docetaxel every 3 weeks at 100mg/m2 dose level.
|
Ref |
Phase, Number of Patients |
Docetaxel |
PSA
Response Rate
>50%
|
Median Response Rate |
Median time to progression or median survival |
(1)*
|
II, 25
|
100 mg/m2 on day 1 of a three week cycle
|
52%
|
|
Median time to progression 4.5 months; median survival 9.3 months
|
(1) D. A. Laber, S. D. Glisson, J. B. Hargis, R. E. Kosfeld, G.
Goldsmith, A. Cervera, R. V. La Rocca,
Phase II study of higher dose docetaxel in androgen independent prostate
cancer. Presented at the 2005 Prostate Cancer Symposium, American Society of
Clinical Oncology, 2005.
*Median PSA at the beginning of the study was 688.4. 25% achieved partial
response,
44% stable disease, 31% progressed. Docetaxel toxicity appears
unacceptable at
this dose and schedule.
Author: Barb Minton, 16 March, 2005.
Updated 17 October 2007 and 20 December 2007 by
H. Hansen
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