|
Update of
Chemotherapy for 2004 - Part I. Taxanes and Mitoxantrone
The following tables
summarize abstracts presented at ASCO 2004 or publications from 2004
pertaining to chemotherapy. In some cases, earlier abstracts and
publications are included for reference. Each table has a list of
references pertaining to that particular table. When new data or
publications come out, this will be updated.
In general, toxicities
have not been included in this paper. They can be found in the
abstracts and papers themselves. In some cases, unique side effects
are mentioned. Another item not included are the pre-medications used with
various chemotherapies. Typically with taxotere, a pulsed dose of dexamethasone is used(e.g.,
8mg the day before, 8 mg day of and 8 mg the day after taxotere), but
the amount varies considerably (e.g., as low as zero to possibly as much as
60mg) depending on the dose schedule of the taxotere.
It should
be noted that in almost all cases dexamethasone is given in a pulsed mode --
either the day of chemotherapy or the day before, day of and day after.
This has been shown to not affect PSA. See Weitzman AL, et al,
Dexamethasone Does Not Significiantly contribute to the Response Rate of
Docetaxel and Estramustine in Androgen-Independent Prostate Cancer, J.
Urology 163:834-837, 2000. They gave patients 20mg for 3 days every 3 weeks
and no patient had a ≥ 50% PSA decline
after dexamethasone and the median PSA increase was 47%. Daily
administration of low dose dexamethasone has shown PSA responses. For
example, Storlie had a 61% RR with 2.25mg daily dexamethasone.
Definitions
-
PSA-RR – A decrease
of more than 50%, sustained for > 4 weeks.
-
M-RR – Measurable
Disease Response Rate.
-
MD - Measurable Disease
(bone mets are not considered measurable).
-
PR - partial response
in measurable disease.
-
CR - complete response
in measurable disease.
-
MDS - Median Duration
of Survival.
-
MTP – Median Time
to Progression.
-
MS – Median
Survival.
-
OS – Overall
Survival.
-
TID - three times a
day.
-
BID - twice a day.
-
qd - every day.
-
Q (or q) - every as in
every 3 weeks (q 3 weeks or q3 w).
There is also interest in combining new biological response modifiers with
various chemotherapeutic agents. The following is a list of some of
these with their generic and brand names. We will include these drugs in an
upcoming paper.
-
Herceptin =
Trastuzumab
-
Gleevec
(STI-571) = Imatinib Mesylate.
PDGFR is present in the
majority of prostate cancers with bone metastases and may be a valid
therapeutic target.
-
Tarceva =
erlotinib, targets a molecule called epidermal growth factor receptor.
-
Iressa =
gefitinib, targets a molecule called epidermal growth factor receptor.
-
Velcade =
bortezomib
-
Trisenox
(arsenic trioxide). Activates proteins that cause tumor cell death and
downregulates Bcl-2, a protein that protects cells from dying. Add vitamin
C to potentiate its effects. Some possible combinations are: Trisenox/velcade/dexamethasone
and Trisenox/taxotere.
Benchmark Taxotere
Phase III trials. Tax327 and SWOG 99-16 were phase III trials that were
completed and published in 2004. They serve as benchmarks for combination
treatments.
| Reference |
Phase and No. of Patients |
Taxotere (Docetaxel) |
Prednisone |
Emcyt |
PSA-RR |
M-RR |
MTP or MS |
| (1)Tannock et al, NEJM 2004. |
III, 335 |
75mg/m2 day 1 of 21 day cycle. (a) |
5mg BID qd |
- |
45% with a median duration of 7.7 mos. |
12% (141) |
MDS 18.9 mos.
MTP 7.7 mos |
| (1)Tannock et al, NEJM, 2004. |
III, 334 |
30mg/m2, days 1, 8, 15, 22 and 29 of a 6
week cycle. (b) |
5mg BID qd |
- |
48% with a median duration of 8.2 mos. |
8% (134) |
MDS 17.4 mos.
MTP 8.2 mos |
| (2)Petrylak et al, NEJM 2004.
|
III, 338 |
60mg/m2 day 2, q21 days. Also, 60mg
dexamethasone in 3 oral divided doses starting evening before and
completed prior to taxotere. |
5mg BID qd |
280mg TID, days 1-5.
(c) |
50% (155/309 patients). |
PR in 17% (17/103 patients) |
Median OS 17.5 mos, MTP 6.3 mos. |
(a) In this arm, patients took dexamethasone 8mg 12 hours, 3
hours and 1 hour before docetaxel infusion (oral). 24mg total.
(b) In this arm, patients took dexamethasone 8mg 1 hour
before docetaxel infusion
(c) Patients had daily warfarin 2mg plus 325mg daily aspirin
as prophylaxic anticoagulation.
(1)Tannock IF, de Wit R, Berry WR, Horti J, Pluzanska A, Chi KN, Oudard S,
Theodore C, James ND, Turesson I, Rosenthal MA, Eisenberger MA; TAX 327
Investigators,
Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced
prostate cancer,
N Engl J Med. 2004 Oct 7;351(15):1502-12.
(2)
Petrylak DP, Tangen CM, Hussain MH, Lara PN Jr, Jones JA, Taplin ME, Burch
PA, Berry D, Moinpour C, Kohli M, Benson MC, Small EJ, Raghavan D, Crawford
ED.,
Docetaxel and estramustine compared with mitoxantrone and prednisone for
advanced refractory prostate cancer;
N Engl J Med. 2004 Oct 7;351(15):1513-20.
Table 1.
Taxotere(Docetaxel) plus Carboplatin and with or without
Estramustine
Phosphate (Emcyt).
|
Reference |
Phase,
No. of patients |
Docetaxel |
Carboplatin |
Emcyt
(b) |
PSA-RR
>50% |
M-RR |
MTP or MS |
|
WK Oh et al (1),
ASCO 2004, # 4656. |
I / 25 |
Day 2, Weekly 3 of
4 weeks. 20, 25, 30, 36, 43 mg/m2 |
AUC 5 |
140mg po TID, days
1-5, 8-12, 15-19 |
60% for All; 75%
at 43mg /m2 |
3 of 14 had PR
(21%) |
MS: 14.6 months. |
|
(2) MH Tay, et al,
ASCO 2004, Abstract 4679 (a) |
- / 4 |
Q 3 week,
60-70mg/m2 |
AUC 4 |
- |
3 of 4 |
- |
OS: >36, 20, 63. |
|
(3) WK Oh, et al, CALGB 99813, Cancer 2003;98:2592-8 |
II / 34 |
Q 3 week,
70mg/m2, day 2.
Used g-csf
support.
|
AUC 5, day 2 following taxotere. |
Emcyt 240mg tid,
days 1-5
|
68% (23 of 34
patients) |
11 of 21 patients,
52% (PR+CR)
|
MDR PSA 10 months.
MDR Measurable 6 months. |
(a) Prior
treatments include D alone in patient 1, MP, epothilone analogue and DE in
patient 2 and DE with bevacizumab in patient 3. This study indicates that
adding carboplatin can continue a response.
(b) Taking Emcyt ,
empty stomach 1 hr before, 2 hr after meals.
(1) W. K. Oh, E.
Hagmann, J. Manola, D. J. George, T. D. Gilligan, M. R. Smith, D. S.
Kaufman, P. W. Kantoff, A phase I study of estramustine,
weekly docetaxel and carboplatin (EDC) chemotherapy in patients
with hormone refractory prostate cancer (HRPC), ASCO 2004, Abstract 4656.
(2) M. H. Tay, D. J.
George, T. D. Gilligan, S. M. Kelly, L. Appleby, M.-E. Taplin, P. G. Febbo,
P. W. Kantoff, W. K. Oh, Docetaxel plus carboplatin (DC) may have
significant activity in hormone refractory prostate cancer (HRPC) patients
who have progressed after prior docetaxel-based chemotherapy, ASCO 2004,
Abstract 4679.
(3) WK Oh et al, A
Phase II Study of Estramustine, Docetaxel, and Carboplatin with
Granulocyte-Colony-Stimulating Factor Support in Hormone-Refractory Prostate
Carcinoma, CLGB 99813;
Cancer 2003;98:2592-8.
Table 2. Docetaxel in combination with high dose calcitriol and with or
without Estramustine Phosphate (Emcyt). (updated
4 Feb 2008.)
|
Reference |
Phase
No.
|
Docetaxel |
HD Calcitriol |
Emcyt
|
PSA-RR
>50% |
M-RR |
MTP or MS |
|
(1) NM Tiffany, et
al, J Urology 2005
(a), (b) |
I/II
24
11 chemo-naïve;
13 prior taxotere |
Q 3 week,
60 mg/m2, 70 mg/m2
after cycle 1.
|
60 mcg. Not dosed
based on body weight. |
Emcyt
280 mg TID, days
1-5 |
Chemo-naïve: 55%
(6 of 11);
1 prior taxotere 9% 1 of
11 |
- |
- |
|
(2) TM Beer, et
al, JCO, Vol 21,2003. |
II, 37, all
chemo-naïve. |
Q weekly, day 2
for 6 weeks of 8 week cycle. 36mg/m2. |
.5 mcg/kg on day
1. |
|
30 of 37 (81%). |
8/15 (53%) had
partial response. |
MTP 11.4 mos., MS
19.5 mos., OS at 1 year 89%. |
| |
|
|
|
|
|
|
|
|
|
(a) 60mcg calcitriol
is a much higher dose than the usual .5mcg/kg of body weight previously used
for weekly dosing.
(b)
Patients also received
325 mg aspirin and 1 or 2 mg warfarin orally daily. Four patients had
thromboembolic complications.
(1) Tiffany NM, Ryan
CW, Garzotto M, Wersinger EM, Beer TM, High dose pulse calcitriol, docetaxel
and estramustine for androgen independent prostate cancer: a phase I/II
study, J Urol. 2005 Sep;174(3):888-92. This was published earlier in
abstract form at ASCO 2004, Abstract 4678.
(2) Tomasz M. Beer, Kristine M. Eilers, Mark Garzotto, Merrill J. Egorin,
Bruce A. Lowe, W. David Henner, Weekly High-Dose Calcitriol and Docetaxel in
Metastatic Androgen-Independent Prostate Cancer; Journal of Clinical
Oncology, Vol 21, Issue 1 (January), 2003: 123-128.
Calcitriol has many interesting properties. Of relevance here is it
role as a chemotherapy sensitizing agent. A list from pre-clinical trial
studies includes:
-
induces cell cycle arrest (G0/G1) and differentiation. (Note: G0 is the
resting phase and G1 is the portion of the cell cycle when RNA and protein
synthesis production starts increasing. )
-
inhibits proliferation of multiple cancer cell lines.
-
downregulates genes that inhibit apoptosis.
-
decreases invasiveness and inhibits angiogenesis.
-
shows synergy with several cytotoxic agents.
Pre-clinical models have their limitations as shown by the study of high
dose calcitriol plus carboplatin where the results did not show any real
improvement over carboplatin alone. See
Beer TM, Garzotto M, Katovic NM. High-dose calcitriol and carboplatin in
metastatic androgen-independent prostate cancer. Am J Clin Oncol. 2004
Oct;27(5):535-41.
Table 3. Docetaxel in
combination with Ketoconazole and
with or without
Estramustine Phosphate (Emcyt).
|
Reference |
Phase
No.
|
Docetaxel |
Ketoconazole |
Emcyt
|
PSA-RR
>50% |
M-RR |
MTP or MS |
|
(1) WD Figg et al,
ASCO 2003, Abstract 1731
(a) |
I, 12 |
3 of 4 weeks,
5mg/m2 MTD with this dose of ketoconazole |
Ketoconazole,
400mg TID + HC
20mg/10mg |
- |
5 of 10 (50%) |
- |
- |
|
(2) PJ Van
Veldhuizen, et al, Cancer 2003. |
I, 26 |
Q21 Days, MTD
55mg/m2 |
Ketoconazole,
400mg BID |
- |
- |
- |
- |
(a) hepatic toxicity.
Going to lowering keto dose, escalating taxotere dose.
(1) W. D. Figg, Y.
Liu, M. R. Acharya, J. L. Gulley, P. M. Arlen, M. Lewis, H. L. Parnes, C. C.
Chen, E. Jones, W. L. Dahut; A phase I trial of high dose ketoconazole plus
weekly docetaxel in metastatic androgen independent prostate cancer; ASCO
2003; Abstract 1731
(2) Van Veldhuizen PJ,
Reed G, Aggarwal A, Baranda J, Zulfiqar M, Williamson S., Docetaxel and
ketoconazole in advanced hormone-refractory prostate carcinoma: a phase I
and pharmacokinetic study; Cancer. 2003 Nov 1;98(9):1855-62.
Table 4. Docetaxel in
combination with Celebrex and
with or without
Estramustine Phosphate (Emcyt).
|
Reference |
Phase
No.
|
Docetaxel |
Celebrex |
Emcyt
|
PSA-RR
>50% |
M-RR |
MTP or MS |
|
(1) B. Kasimis, et
al; ASCO 2004, abstract 4616.
|
II, 18 |
3 of 4 weeks,
30mg/m2 |
400mg po BID |
- |
11/17
(64.7%) |
5/ (2CR's + 3PR's)
(29.4%); SD in 5pts(29.4%) |
- |
(1) B. Kasimis, J.
Cogswell, S. Hwang, V. Chang, M. Llorente, I. Boholli, S. Srinivas, E.
Morales, C. Davis, M. Blumenfruchtl; Phase II trial of docetaxel (D) and
high-dose celecoxib (C) in patients (Pts) with hormone resistant prostate
cancer (HRPC); ASCO 2004, Abstract No: 4616
Table 5. Docetaxel in
combination with Mitoxantrone and with or without
Estramustine Phosphate (Emcyt).
|
Reference |
Phase
No.
|
Docetaxel |
Mitoxantrone |
Emcyt
|
PSA-RR
>50% |
M-RR |
MTP or MS |
|
(1)Heidenreich, A,
et al, ASCO 2003, Abstract 1655.
|
II, 72 |
Q 3 weeks; 60mg/m2 |
8 mg/m2. |
- |
42 (62%); 15 (22%)
stable PSA. |
- |
- |
(1) A. Heidenreich,
S. Carl, S. Gleissner, O. Moormann; Docetaxel (DOC) and mitoxantrone (MIT)
in the management of hormone-refractory prostate cancer (HRPC), ASCO 2003,
Abstract 1655.
There are also two
other abstracts on this combination from the AUA 2003 meeting:
Heidenreich,Axel et
al, Mitoxantrone and Docetaxel, AUA 2003 abstract # 1491. Asymptomatic
hrpca men with rising PSAs. This is the same study as in (1).
Beer TM et al, AUA
2003 abstract # 1662, mitoxantrone/docetaxel before RP for high risk men.
MTD was 35mg/m2 taxotere with 4mg/m2 mitoxantrone on a 3 weeks out of 4
dosing schedule.
Table 6. Docetaxel in combination with Estramustine Phosphate (Emcyt).
|
Reference |
Phase and no. of
patients
|
Docetaxel |
Emcyt |
PSA-RR
>50% |
M-RR |
MTP or MS |
|
(1) K Miller et
al. ASCO 2003, Abstract 1660. (a)
|
II, 49 |
35mg/m2 3 of 4
weeks on days 2, 9, 16. |
140mg TID, days
1-3, 8-10, 15-17. |
32/44 (73%)
patients achieved a partial PSA response, and 10 patients showed a
complete PSA decline (PSA normalization). Pain decreased by >50% in 26
patients. |
- |
- |
|
(2) R. Birch et
al, ASCO 2004, Abstract 4622. |
IIb, 62, split arm
A and B.
Chemo-naïve. |
Arm A: D 36 mg/m2
IV day 2, 9, 16, 23, 30, 37 q 8 wks |
Arm A: E 280 mg/m2
day 1-5 and day 22-26 PO
|
11/21 evaluable
patients (52%) in arm A. |
|
Median overall
survival was 16.4 months in arm A |
|
Arm B: D, 70 mg/m2
IV day 2 q 3 weeks. |
Arm B: E 280 mg/m2
day 1-5 PO. |
19/29 evaluable
patients (66%) in arm B. |
|
Median overall Survival,
13.2 months in arm
B |
|
(3)JC
Eymard, et al. ASCO 2004, abstract 4603. |
II,
92, randomized to 48 in arm A and 44 in arm B. |
Arm A (70 mg/m2 IV over 1 hour d1 q3weeks
|
560 mg/d PO starting 1 day prior to D, for 5 consecutive
days). |
PSA decrease
>50%: 68%;
PSA
decrease
>75%: 36%. |
MD: 40 pts. PR 18.2% (Arm A)
|
Median PSA
Response duration, 6 mos.
MTP 5.7 mos (range 4.7-5.8) |
|
Arm B (75 mg/m2 IV over 1 hour d1 q3w)
|
- |
PSA decrease
>50%: 29%;
PSA
decrease
>75%: 16% |
MD: 40 pts.
PR 16.7% (Arm B). |
Median PSA
Response duration, 6 mos.
MTP 2.8 mos (2-6.9) |
|
(3)
DM Saverese et al,
CALGB 9780. J Clin Oncol. 2001 May 1;19 (9):2509-16 |
II, 46 |
70mg/m2 q 3 weeks.
Hydrocortisone qd 30mg am, 10mg pm.
|
10mg/kg/d total dose divided TID, days 1-5 |
30/44 68% |
12/24 50% (CR (13%)+ PR (38%)). Median PSA decline
of 99.5% |
Median Overall survival 20 mos., MTP 10 mos for
patients w/MD and 7 mos bone only. |
|
(4) VJ Sinibaldi, Cancer 2002. |
II, 42. 10 (25%) had
previous chemotherapy |
Q21 days, 70mg/m2 |
280 mg orally every 6 hours × 5 doses) every 21
days. Total dose is 1400mg over 24 hours. 0-6-6-6-6 hr intervals. |
18/40, 45% |
4/20, 20% PR |
MTP 4 mos. MS 13.5 mos for all patients. |
(a) they don’t
mention the results for a PSA RR >50%.
(1)
K. Miller, U. Steiner, S. Machtens, B. Backhaus, M. Siegsmund, M. Johannsen,
C. Wulfing, Combination chemotherapy with weekly docetaxel and intermittent
estramustine in patients with hormone-refractory prostate cancer (HRPC): A
multicenter phase II study; ASCO 2003, Abstract No: 1660.
(2) R. Birch, L.
Kalman, L. Holt, B. Graham, B. Wheeler, L. Schwartzberg, Randomized phase
IIb trial comparing two schedules of docetaxel (D) plus estramustine (E) for
metastatic hormone refractory prostate cancer (HRPC); ASCO 2004,
Abstract No: 4622.
(3)J.-C. Eymard,
F. Joly, F. Priou, A. Zannetti, A. Ravaud, P. Kerbrat, M. Mousseau, B. Paule,
F. Touze, E. Ecstein-Fraisse; Phase II randomized trial of docetaxel plus
estramustine (DE) versus docetaxel (D) in patients (pts) with
hormone-refractory prostate cancer (HRPC): A final report; ASCO 2004,
Abstract 4603.
Note:
Prophylactic warfarin (1mg/d PO) was given continuously in
Arm A.
(4)
Savarese DM, Halabi S,
Hars V, Akerley WL, Taplin ME, Godley PA, Hussain A, Small EJ, Vogelzang NJ;
Phase II study of docetaxel, estramustine, and low-dose hydrocortisone in
men with hormone-refractory prostate cancer: a final report of CALGB 9780.
Cancer and Leukemia Group B.J Clin Oncol. 2001 May 1;19(9):2509-16.
Note on patient entry
demographics: Location of metastases(a patient may have had more than one
site).
Bone: 37(80%); Lymph node
involvement: 23 (50%); Lung: 4 (9%); Liver: 2 (4%). Measurable disease
(mostly lymphadenopathy: 24 (52%).
Note on thrombosis events: 4 (9%), 1 arterial
embolism, 1 DVT, 2 superficial venous thrombophlebitis.
(5)Sinibaldi, Victoria J.; Carducci, Michael A.; Moore-Cooper, Sandra; Laufer, Menachema; Zahurak,
Marianna; Eisenberger, Mario A., Phase II evaluation of docetaxel plus one-day oral estramustine phosphate in the treatment of patients with
androgen independent prostate carcinoma; Cancer 2002;94:1457–65.
Table 7. Docetaxel in combination with Avastin and with or without
Estramustine Phosphate(Emcyt). Avastin is bevacizumab (a
humanized murine monoclonal antibody to the vascular endothelial growth factor,
or anti-VEGF). A phase III version of this may have started, with q 3 weekly
taxotere and prednisone plus avastin. 850 patients planned.
| Reference |
Phase and No. of patients |
Docetaxel |
Avastin (beva-cizumab) |
Emcyt |
PSA-RR >50% |
M-RR |
MTP or MS |
| (1)J. Picus et al, CALGB 90006, ASCO
2003, abstract 1578 |
II, 79.
Chemo-naive. |
70
mg/m2 IV on day 2, and repeated every 21 days. |
15 mg/kg of B on
day 2 |
280mg po TID for
days 1-5 |
79% |
58% |
TTP: 9 mos |
| |
|
|
|
|
|
|
|
(1) J. Picus, S.
Halabi, B. Rini, N. Vogelzang, Y. Whang, E. Kaplan, W. Kelly, E. Small; The
use of bevacizumab (B) with docetaxel (D) and estramustine (E) in hormone
refractory prostate cancer (HRPC): Initial results of CALGB 90006; ASCO
2003, Abstract No: 1578.
Note on toxicity:
No major bleeds occurred, one patient died of mesenteric vein thrombosis, and one other
patient had a deep vein thrombosis. One patient had a stroke. Another
patient died from a perforated sigmoid colon thought to be unrelated to
treatment.
Table 8. Taxotere (Docetaxel)
in combination with Xeloda (capecitabine) and with or without Estramustine
Phosphate (Emcyt). Xeloda
(capecitabine) is a pro-drug (chemical that turns into the active drug once
it is in the circulation) of 5-FU, a very potent chemotherapeutic that is
also very toxic. Capecitabine seems to be able to get the same level of
effectiveness as 5-FU without much of the gastrointestinal toxicity.
|
Reference |
Phase and No. of
Patients |
Docetaxel |
Xeloda (capecitabine) |
Emcyt |
PSA-RR |
M-RR |
MTP or MS |
| (1)J. Ferrero, et al, ASCO 2004, Abstract
#4624. |
II, 23 of 50 planned patients.
Prior emcyt use allowed. |
35mg/m2, days 1, 8, 15 |
1250mg/m2/day in 2 divided doses from day
5 to 18 of each 28 day cycle. |
- |
Biological response was observed in 17 pts after the 2nd
cycle and in 7 pts after the 4th cycle. Seven pts (41.2%)
exhibited a PSA decrease of >50% after the 2nd cycle and 5
pts (71.4%) after the 4th cycle. |
- |
- |
| (2) R Morant, et al., BJC 2004. |
II, 25 |
- |
1250 mg m(-2) orally twice daily on days 1-14 every 21 days.
Based on toxicity data, they recommend a lower starting dose of
1000 mg x m2 orally twice daily. |
- |
3 (12%); response duration was 12, 17 and
32 weeks. |
- |
median time to tumour progression of all
patients was 12 weeks |
(1)J.
Ferrero, J. F.
Berdah, E. Chamorey, S. Oudard, S. Dides, G. Lesbats, G. Cavaglione, P.
Nouyrigat, C. Foa, P. Guillet, R. Kaphan;
A combination docetaxel-capecitabine in patients (pts) with
hormone refractory advanced prostate cancer. ASCO 2004, abstract
4624.
Two other references on
Xeloda as a single agent for hrpca are:
(2) Morant R, Bernhard J,
Dietrich D, Gillessen S, Bonomo M, Borner M, Bauer J, Cerny T, Rochlitz C,
Wernli M, Gschwend A, Hanselmann S, Hering F, Schmid HP.; Capecitabine in
hormone-resistant metastatic prostatic carcinoma - a phase II trial; Br J
Cancer. 2004 Apr 5;90(7):1312-7. They concluded that xeloda should be
combined with vinorelbine or docetaxel to be more effective.
(3) El-Rayes BF, Black CA, Ensley JF., Hormone-refractory
prostate cancer responding to capecitabine; Urology. 2003
Feb;61(2):462. This is a case report. 5 months of Xeloda resulted in
a complete clinical response.
Table 9. Taxotere +
Navelbine(vinorelbine).
Vinorelbine, a semisynthetic vinca alkaloid, and docetaxel, a
semisynthetic taxane, are active single agents in hormone-refractory prostate
cancer and have demonstrated synergy in tumor cell lines and animal models.
They both are anti-microtubular. Tumors are sensitized to taxanes
by increasing the percentage of tumor cells in the G2/M phase of the cell cycle
and vinorelbine is capable of G2/M arrest, so the combination may create a
salvage treatment also. Vinorelbine might also be combined with taxol.
|
Reference |
Phase and No.of
patients |
Taxotere |
Navelbine
(vinorelbine) |
Emcyt |
PSA-RR |
M-RR |
MTP or MS |
|
(1) AJ Koletsky et al; Cancer J. 2003.
(a) |
II, 21 Chemo-naive. |
25 mg/m2 after vinorelbine. |
vinorelbine, 20 mg/m2, followed by docetaxel
on days 1 and 8 of a 21-day cycle. |
- |
19 patients were evaluable.
> 75%, 8 patients;
≥ 50% to
≤ 75%, 3 patients;
< 50%, 7 patients |
5 had MD, 3 evaluable,
1 CR + 2 PR. |
- |
| (2)CJ Sweeney et al, Ann. Onco. 2002. (b) |
II, 23 |
- |
Weekly 20 mg/m2 (or
15 mg/m2 if a history of prior pelvic radiotherapy). After 8
weeks of therapy the combination was given every other week. |
280 mg orally TID for 3 days
(the day before, the day of and the day after vinorelbine infusion). |
15/21 (71%) |
1/8 (12.5%) PR. |
MTP (serologic) 3.5 mos. Estimated MS
15.1 mos, actual 1 yr overall survival 71%. |
| (3) S Goodin et al, ASCO 2002, abstract
2459. |
II, 30 With and
without prior chemotheapy(c).
g-csf support days 2-6, 9-13. |
60mg/m2 day 1 |
15mg/m2 days 1 and 8 of 21 day cycle. |
|
20 mean decrease 57.1% (25.8-90.6%)
Chemo-naive: 7(44%) >50% decrease and 5 had stable
disease.
Prior chemo: 4/14 (29%) demonstrated a > 50% decrease in PSA (2
that progressed on prior chemo and 2 with prior adjuvant chemo). |
- |
Mean duration of PSA response 6.1
mos(1-18 mos). |
| Other dosing
schedules |
None; tailored to
the patient. |
2nd 20mg/m2 weekly. |
1st 10mg bolus. gm-csf
support. |
- |
- |
- |
- |
| 20mg/m2 3 of 4 weeks or 2 wks
on/1 off, repeat q21 days. |
20mg/m2 3 of 4 weeks or 2 wks
on/ 1 off repeat q21 days. |
- |
- |
- |
- |
| 25mg/m2 day 3. |
5-10mg/m2 x 3 days. |
- |
- |
- |
- |
(a) g-csf was used as needed.
(b) 48% lower extremity edema and 17% thromboembolic events (emcyt probable
cause). No indication of anticoagulation.
(c) 14 patients had prior
chemotherapy; 9 had progressed on chemotherapy of which 5 with prior taxane and 5
had received chemotherapy in the adjuvant setting of stage D0 disease.
(1) Koletsky AJ, Guerra ML, Kronish L., Phase II study of vinorelbine and
low-dose docetaxel in chemotherapy-naive patients with hormone-refractory
prostate cancer, Cancer J. 2003 Jul-Aug;9(4):286-92. Erratum in: Cancer J. 2003
Sep-Oct;9(5):1 p following table of contents.
(2)
Sweeney CJ, Monaco FJ, Jung SH, Wasielewski MJ, Picus J, Ansari RH, Dugan WM,
Einhorn LH., A phase II Hoosier Oncology Group study of vinorelbine and
estramustine phosphate in hormone-refractory prostate cancer., Ann Oncol. 2002
Mar;13(3):435-40.
(3)
Susan Goodin, Kamakshi V Rao, Elizabeth A Engle, Michael Kane, Terry Capanna,
Marie Ciardella, Mary B Todd, Robert S DiPaola,
A phase II study of docetaxel and vinorelbine in hormone refractory prostate
cancer (HRPC) with and without prior chemotherapy;
2002 ASCO Annual Meeting, Abstract 2459.
There are other possible combinations with vinorelbine as discussed in the
following paper:
(4)
Willi Kreis, A. Calabro, D.R. Budman, L.M. Adams, North Shore University
Hospital, Manhasset, NY.
Synergy of Navelbine (Vinorelbine) with Conventional Chemotherapeutic Agents in
Human Prostate Cancer Cell Lines in Vitro. 2375, year 2001. They found
vinorelbine was synergistic with docetaxel or doxorubicin and suggested that
vinorelbine in combination with anthracyclines and anti-tubulin agents was
warranted.
The
paper indicates possibilities, not clinical data.
Table 10. Taxotere (Docetaxel) and Thalidomide with or without Estramustine
Phosphate (Emcyt).
| Reference |
Phase and No. of Patients |
Taxotere |
Thalidomide |
Emcyt |
PSA-RR |
MD-RR |
MTP or MS |
| (1)RC Frank et al, ASCO 2004, abstract
4681. (a) |
II, 12 as of abstract.
6 months of TET, followed by 6 mos thalidomide alone as
maintenance.
|
25mg/m2 3 of 4 weeks. |
100 or 200mg as tolerated. |
140mg po tid, day
before, day of and day after taxotere. |
>50% 6/9 (67%), >75% in 4/9 (44%), and normalized in 2/9
(22%). |
5 pts with measurable disease, 2 had PR (40%) and 2 SD. |
- |
| (2)WL Dahut et al, JCO 2004.
(b) |
II, 75, chemo
-and thalidomide
naive. |
30mg/m2 3 of 4 weeks, 25 patients.
|
-
|
| |
