A phase II study of escalated-dose docetaxel with granulocyte colony-stimulating factor support in patients with advanced breast cancer

P. L. R. Mitchell1,*, R. Basser2, M. Chipman1, A. Grigg3, R. Mansfield3, J. Cebon1, I. D. Davis1, F. Appia4 and M. Green3

Centre for Developmental Cancer Therapeutics (CDCT), 1 Austin Hospital, 2 Western Hospital and 3 Royal Melbourne Hospital, Melbourne, Australia; 4 Aventis, Melbourne, Australia and Paris, France

Received 28 July 2003; revised 22 December 2003; accepted 31 December 2003


    ABSTRACT
 Top
 ABSTRACT
 Introduction
 Patients and methods
 Results
 Discussion
 REFERENCES
 
Purpose:

Docetaxel is highly active in the treatment of patients with breast cancer. The principal dose-limiting toxicities of the 3-weekly regimen are neutropenia and febrile neutropenia. In a previous phase I dose-escalation study with granulocyte colony-stimulating factor (G-CSF) support, the recommended dose was determined to be docetaxel 160 mg/m2 3-weekly. The objectives of this phase II study were to determine the response rate and toxicity of this dose and schedule, given as first-line in patients with advanced breast cancer. Mobilisation of peripheral blood stem cells (PBSCs) was also investigated.

Patients and methods:

Eligible women had metastatic breast cancer and were aged 18–75 years with ECOG performance status ≤2. Strict criteria for liver function were followed, and adjuvant chemotherapy must have been completed at least 6 months previously. Treatment was docetaxel 160 mg/m2 over 60–90 min every 21 days with G-CSF 5 µg/kg/day until neutrophil recovery, for up to six cycles. A 3-day corticosteroid prophylaxis was given. Bloods samples to determine PBSC levels [CD34+, granulocyte–macrophage colony-forming cells (GM-CFC) and burst-forming units-erythroid (BFU-E)] were taken on days 6, 8, 9 and 11 following docetaxel.

Results:

Twenty-five women with median age 50 years (range 35–66) were included. Seventeen (68%) had previously received adjuvant chemotherapy. In total, 112 cycles were delivered (median four per patient), with dose reductions required in 12.5% of cycles. G-CSF was given for a median of 6 days. The median neutrophil nadir was 0.5 x 109/l and occurred a median 5 days after treatment. The median duration of grade 3 or 4 neutropenia was 2 days (range 1–7). Grade 4 neutropenia occurred in 44% of patients, but there was only one episode of febrile neutropenia. Five patients were taken off study due to toxicities that included oedema, neurosensory toxicity and asthenia. Confirmed partial response was seen in nine patients (37.5%; 95% confidence interval 19% to 59%). CD34+ cells, GM-CFC and BFU-E levels peaked at day 8 following docetaxel administration. The median CD34+ cell peak was 6.5 x 104/ml, with only 20% of patients <2 x 104/ml, a level below which leukapheresis is not usually attempted.

Conclusions:

Docetaxel 160 mg/m2 was delivered with G-CSF support with a very low rate of febrile neutropenia. Non-haematological toxicity was significant, causing five patients to go off study. Effective mobilisation of PBSCs was seen. The response rate of 37.5% was less than that obtained in first-line studies using standard-dose docetaxel 100 mg/m2, suggesting that there is no additional benefit in dose escalation of this cytotoxic agent in breast cancer patients using this schedule.

Key words: breast cancer, docetaxel, dose escalation, G-CSF, mobilisation, peripheral blood stem cells, phase II trial, toxicity


    Introduction
 Top
 ABSTRACT
 Introduction
 Patients and methods
 Results
 Discussion
 REFERENCES
 
Docetaxel is a semi-synthetic taxoid that is active against a wide range of malignancies. From phase I studies, the recommended dose of 3-weekly docetaxel was found to be 100 mg/m2 given over 1 h, and the principal dose-limiting toxicity (DLT) was neutropenia [1, 2]. In a previous phase I dose-escalation study of docetaxel with granulocyte colony-stimulating factor (G-CSF) support, we determined the recommended dose for phase II studies as 160 mg/m2. With doses between 110 and 170 mg/m2, grade 4 neutropenia occurred in 35% of patients and febrile neutropenia in only 10%. Non-haematological toxicities, including skin and neurosensory, were dose limiting [3].

Docetaxel is the most active single agent in breast cancer, and at standard doses of 100 mg/m2 produces response rates of 48–61% given first-line as a single agent [46], and 30%–42% given second-line following anthracycline failure [79]. This study investigated whether escalated-dose docetaxel, given with G-CSF support to reduce neutropenia and febrile neutropenia, would result in higher response rates in patients treated first-line. In addition, we assessed toxicity and investigated the mobilisation of peripheral blood stem cells (PBSCs) with this regimen.


    Patients and methods
 Top
 ABSTRACT
 Introduction
 Patients and methods
 Results
 Discussion
 REFERENCES
 
Patients
The trial was carried out by the Centre for Developmental Cancer Therapeutics (CDCT) research group in Melbourne, Australia, with participation of Austin, Royal Melbourne and Western Hospitals.

Women with histologically or cytologically proven breast cancer were eligible, aged 18–75 years and with ECOG performance status (PS) ≤2. Baseline neurosensory changes were required to be grade ≤1, neutrophils ≥1.5 x 109/l, platelets ≥100 x 109/l, haemoglobin ≥10 g/dl and serum creatinine <1.5 times the institutional upper normal limit (UNL).

The eligibility criteria for hepatic function were as follows: total bilirubin ≤1x UNL, or ≤1.5x UNL if aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP) were normal; AST and ALT ≤2.5x UNL; and ALP ≤5x UNL (except in absence of liver metastases and presence of bone disease). Patients with both ALP >2.5x UNL and AST or ALT >1.5x UNL were not eligible.

Patients were allowed to have received adjuvant chemotherapy if it was completed at least 6 months previously, but were not to have received chemotherapy for advanced or metastatic disease. Patients were not to have received prior docetaxel or high-dose chemotherapy requiring haematopoietic progenitor support. Prior hormonal therapy or radiotherapy must have been completed at least 4 weeks previously, and total radiotherapy must have been to ≤30% of marrow-bearing areas. Patients with significant psychiatric or medical illnesses were not eligible. Patients gave written informed consent and the study was approved by the institutional ethics committees of participating hospitals.

At baseline the following investigations were undertaken: history and physical examination; electrocardiogram; complete blood count (CBC); electrolytes; renal and hepatic function; calcium; and random glucose. The CBC was checked three times per week from day 5 until neutrophil recovery, and then weekly. Baseline imaging investigations included a chest X-ray, a computed tomography scan of disease sites, and other imaging as required. Imaging of disease sites was repeated after three and six cycles. Objective responses were to be confirmed after at least 4 weeks.

Blood for peripheral blood stem cell (PBSC) assays was taken during cycle 1, at baseline, and on days 6, 8, 9 or 10 and 11 following treatment. Assays of CD34+ cells, granulocyte–macrophage colony-forming cells (GM-CFC) and burst-forming units-erythroid (BFU-E) were carried out as described previously [10].

Treatment and study design
The primary end point of the study was response rate, and secondary end points were toxicity and PBSC assays. A sample size of 25 patients was chosen for this exploratory study, to give preliminary information on response rate and to investigate whether this regimen could be delivered safely.

Patients received docetaxel 160 mg/m2 as a 1 h infusion every 3 weeks, for up to six cycles. The infusion duration was increased to 90 min where individual doses were >240 mg. A total of six doses of oral dexamethasone 8 mg were given at the following times: the evening prior to treatment; the morning of, and 1 h prior to, treatment; the evening after treatment; and the morning and evening of the next day.

Patients received G-CSF (lenograstim; Aventis, Paris, France) 5 µg/kg as a daily subcutaneous injection, commencing the day after chemotherapy and continuing until neutrophils were ≥1.0 x 109/l.

Toxicities were graded using the National Cancer Institute common toxicity criteria criteria, version 1.0. Docetaxel was administered every 21 days provided the neutrophil count was ≥1.5 x 109/l and platelets ≥100 x 109/l. Dose reductions of 20 mg/m2 were made for the following toxicities: febrile neutropenia persisting for ≥3 days despite intravenous antibiotics; platelet nadir <25 x 109/l; grade ≥3 skin toxicity or grade ≥2 neuropathy. Patients with persisting grade ≥2 skin or neurosensory toxicity after 1 week’s delay were to go off study. If grade ≥3 nausea, vomiting or diarrhoea occurred, patients received appropriate prophylaxis for the next cycle, and if grade ≥3 toxicity recurred a 20 mg/m2 dose reduction was made. If bilirubin became elevated above the baseline level, patients went off study if this did not recover to baseline by day 28. A 25% dose reduction occurred for abnormal hepatic function (AST and/or ALT ≥2.5x UNL or ALP ≥2.5x UNL) measured at the time treatment was due. With AST and/or ALT >5x UNL or ALP >5x UNL, 1 week was allowed for recovery to below these levels, after which time patients without recovery went off study. Other grade 3 or 4 toxicity required delay until recovery to grade ≤1, and a 10 mg/m2 dose reduction was subsequently made. No dose reductions were made for allergic reactions, peripheral oedema or effusions, or alopecia.

Complete and partial responses (PRs) were assessed using standard WHO criteria for bidimensional measurements. Response assessment was carried out by the investigators. Peak CD34+, GM-CFC and BFU-E cell levels from chemonaïve patients and those who had previously received chemotherapy were compared using the Mann–Whitney U-test.


    Results
 Top
 ABSTRACT
 Introduction
 Patients and methods
 Results
 Discussion
 REFERENCES
 
Twenty-five patients were enrolled on study. All were evaluable for toxicity and 24 were evaluable for efficacy (Table 1). The median age was 50 years (range 35–66) and all had PS 0–1, except for four patients (16%). Metastatic disease was extensive in most patients, with 18 (72%) having three or more metastatic sites. Thirteen patients (52%) had liver metastases. Seventeen patients (68%) had previously received adjuvant chemotherapy, which for 12 patients (48%) had included anthracyclines. No patients had received paclitaxel.


View this table:
[in this window]
[in a new window]
 
Table 1. Patient characteristics (n = 25)
 
Treatment
Patients received a median of four cycles of docetaxel (range one to six), with the median total dose delivered of 648 mg/m2 (range 157–967). The median dose intensity was 52 mg/m2/week (range 43–54), which was 98% of that predicted. A total of 112 cycles was delivered, with four patients requiring dose reductions for 14 cycles (12.5%). Dose reductions were due to non-haematological toxicity: neurosensory toxicity in three patients and myalgia in one patient. Treatment was administered at the planned 3-weekly interval, except for eight cycles (7%) with dose delay.

Five patients (20%) discontinued treatment due to toxicity, with discontinuation after four cycles for four patients and after five cycles for one patient. Toxicity was grade 3 asthenia (one patient), grade 3 neurosensory (one patient), grade 3 peripheral oedema (one patient), grade 2 asthenia and grade 3 peripheral oedema (one patient), and grade 3 asthenia, neurosensory and neuromotor toxicity (one patient). There were no treatment-related deaths.

Haematological toxicity
G-CSF was administered for a median of 6 days (maximum 9 days). The median neutrophil nadir was 0.5 x 109/l (range 0–5.1), which occurred a median 5 days (range 5–6) after docetaxel administration. Eleven patients (44%) developed grade 4 neutropenia at some time during the course and an additional five patients (20%) developed grade 3 neutropenia (Table 2). The median duration of grade 3 or 4 neutropenia was 2 days. There was no grade 3 or 4 thrombocytopenia, and the median platelet nadir was 132 x 109/l, occurring at a median of 6 days after treatment. Anaemia was infrequent and no worse than grade 2, seen in two patients (8%), one of whom required transfusion. There was only one episode of febrile neutropenia. An additional two patients had grade 3 infection without neutropenia (Table 2).


View this table:
[in this window]
[in a new window]
 
Table 2. Adverse events in 25 patients
 
Non-haematological toxicity
The most frequent grade 3 or 4 non-haematological toxicity was asthenia, which was grade 3 in nine patients (36%). An additional 10 patients (40%) had grade 2 asthenia. Grade 3 peripheral oedema occurred in six patients (24%). Neurosensory toxicity was frequent, with three patients (12%) having grade 3 and 11 patients (44%) having grade 2 toxicity. Eleven patients (44%) had grade 2 or 3 nail toxicity (Table 2).

Antitumour efficacy
The median time to progression (TTP) was 163 days. Twenty-four patients were evaluable for efficacy. Confirmed PR was seen in nine patients [37.5%; 95% confidence interval (CI) 19% to 59%]. An additional two patients (8.3%) obtained an unconfirmed PR, for a combined confirmed and unconfirmed PR rate of 46% (95% CI 26% to 66%). Of the patients with PR or unconfirmed PR, eight patients (73%) had received prior adjuvant chemotherapy, compared with nine patients (64%) having received adjuvant chemotherapy in the non-responder group. Amongst responding patients, five patients (45%) had previously received adriamycin compared with seven (50%) of the non-responders.

PBSC assays
PBSC assay results were available for 20 patients. The results are shown in Table 3. Peak CD34+, GM-CFC and BFU-E cell levels occurred at day 8 following docetaxel and G-CSF.


View this table:
[in this window]
[in a new window]
 
Table 3. Peripheral blood stem cell assaysa
 
The median peak CD34+ cell level was 6.5 x 104/ml (range 0.3–22). Sixteen of 20 patients (80%) had peak CD34+ ≥2.0 x 104/ml, a level above which leukapheresis is associated with adequate PBSC yields [11, 12]. The median peak CD34+ cell level was 4.6 x 104/ml (range 0.8–16.2) for patients with prior adjuvant chemotherapy, and 10.9 x 104/ml (range 1.7–2.2) for no adjuvant chemotherapy (P = 0.15). Three of the four patients with peak values <2 x 104/ml had received adjuvant chemotherapy, which may have affected PBSC mobilisation.


    Discussion
 Top
 ABSTRACT
 Introduction
 Patients and methods
 Results
 Discussion
 REFERENCES
 
Docetaxel has become a widely used cytotoxic agent for a range of malignancies. It is the most active single agent in breast cancer [6], and is effective in the first-line setting as well as in anthracycline failures [49]. More recent data support efficacy in the neo-adjuvant and adjuvant treatment of patients with primary disease [13, 14].

Despite widespread usage in breast and other malignancies, the potential for dose escalation of docetaxel has not been explored systematically. We previously reported a dose-escalation study in patients with a range of malignancies, where docetaxel was escalated in 10 mg/m2 increments with G-CSF support. DLTs were skin and neurosensory, and the recommended dose for phase II studies was 160 mg/m2 given every 3 weeks [3].

In the current study, docetaxel was administered at 98% of the planned dose intensity. Dose reductions were required in only 12.5% of cycles, and only 7% of cycles were delayed. These data confirm that it is feasible to deliver docetaxel 160 mg/m2 with G-CSF support to this patient population. The current study was notable for a very low level of febrile neutropenia, with only one episode of febrile neutropenia when prophylactic G-CSF is given. This confirms the results of our previous phase I study, where only two of 29 patients developed febrile neutropenia. In the current study, although 11 patients (44%) had grade 4 neutropenia, the median duration was only 2 days. The duration of neutropenia is known to be a significant factor in the risk for developing infection [15]. Studies of standard-dose docetaxel with G-CSF in a range of malignancies have also generally shown a low rate of febrile neutropenia [16, 17], although in one study of 60 patients with lung cancer a febrile neutropenia rate of 30% was seen [18].

The pattern of non-haematological toxicity was similar to that seen for patients treated at standard doses and similar to the profile seen in our previous phase I trial [3]. Peripheral oedema and asthenia were the most troublesome toxicities, and led to cessation of treatment in four patients. These toxicities became more apparent with multiple cycles. Three patients had grade 3 neurosensory toxicity, leading to cessation in two patients. Toxicity to nails was frequent and consisted of marked discolouration and onycholysis. Cutaneous toxicity was frequent and seen in 72% of patients, which was higher than in some studies of standard-dose docetaxel [8]. However, severe cutaneous toxicity did not occur, which is also usually the case with standard dose docetaxel [8]. This is interesting, as cutaneous toxicity was dose-limiting in the phase I study of this regimen [3].

Overall, 37.5% (95% CI 19% to 59%) of patients had objective responses, which were all PRs. An additional 8.3% of patients had unconfirmed PRs. Prior adjuvant chemotherapy, with or without adriamycin, did not appear to influence the response rate. The response rate is less than the 54–61% response rate obtained in phase II studies of docetaxel 100 mg/m2 in first-line treatment of advanced breast cancer [4, 5]. It is also less than the 48% response rate to docetaxel 100 mg/m2 obtained in a randomised trial reported by Chan et al. [6] comparing docetaxel with doxorubicin in a population previously treated with alkylating agents, 49% of whom had received chemotherapy for metastatic disease. There was also no improvement in TTP seen with escalation of the dose of docetaxel. The TTP was 23 weeks in the current study, compared with 26 weeks in the study by Chan et al. [6].

Paclitaxel shares a similar cytotoxic mechanism with docetaxel and is active against a similar spectrum of malignancies. Dose escalation of paclitaxel in breast and other malignancies has sometimes improved response rates, but without clear improvement in survival or other end points. In a randomised study, Winer et al. [19] assigned 325 women with metastatic breast cancer to paclitaxel 135, 210 or 250 mg/m2 over 3 h. No difference was seen in response rate or overall survival. Similarly, in a study of 471 women randomised to paclitaxel 135 or 175 mg/m2 over 3 h, no significant difference in response rate or survival was seen [20]. In ovarian cancer, increases in paclitaxel dose from 135 to 175 mg/m2 [21] or 135 to 250 mg/m2 [22] have resulted in small increases in response rate, but no improvement in survival. Likewise, escalation of paclitaxel from 135 to 250 mg/m2, in combination with cisplatin, did not improve response rate or survival in patients with non-small-cell lung cancer [23].

Previous studies have reported mobilisation of PBSC using docetaxel 100 mg/m2 [24, 25] or 100–120 mg/m2 [26] along with G-CSF 10 µg/kg/day. In a study of docetaxel 100 mg/m2 and G-CSF 10 µg/kg/day, the kinetics of PBSC mobilisation were similar to the current study, with peak CD34+ cell levels occurring on days 8 and 9 [24]. In the current study, 80% of patients achieved a peak CD34+ cell level >2 x 104/ml, a level that is associated with sufficient PBSC collection at leukapheresis [11, 12]. Peak levels of GM-CFC and BFU-E were similar to those obtained from our institution following cyclophosphamide 2 g/m2 and G-CSF as a mobilising regimen, using the same techniques in the same laboratory (data not shown).

In this study of patients with breast cancer treated first-line, docetaxel 160 mg/m2 was safely delivered every 3 weeks with G-CSF support. Febrile neutropenia was infrequent, but non-haematological toxicities, especially peripheral oedema and asthenia, were significant for some patients. The response rate of 37.5% was less than that seen in phase II and III studies of standard-dose 3-weekly docetaxel given first-line. These results suggest that escalation of the dose of docetaxel to 160 mg/m2 using this schedule is unlikely to improve patient outcomes.


    Acknowledgements
 
The authors acknowledge Dr Glenn Begley for input into the manuscript. This study was supported in part by Aventis Pharmaceuticals.


    FOOTNOTES
 
* Correspondence to: Dr P. Mitchell, Austin Hospital, Studley Road, Heidelberg, Melbourne, Victoria 3084, Australia. Tel: +61-3-9496-3546; Fax: +61-3-9496-3379; E-mail: paul.mitchell{at}austin.org.au Back


    REFERENCES
 Top
 ABSTRACT
 Introduction
 Patients and methods
 Results
 Discussion
 REFERENCES
 
1. Burris H, Irvin R, Kuhn J et al. Phase I clinical trial of taxotere administered as either a 2-hour or 6-hour intravenous infusion. J Clin Oncol 1993; 11: 950–958.[Abstract]

2. Extra JM, Rousseau F, Bruno R et al. Phase I and pharmacokinetic study of taxotere (RP 56976; NSC 628503) given as a short intravenous infusion. Cancer Res 1993; 53: 1037–1042.[Abstract]

3. Mitchell PLR, Basser R, Chipman M et al. A phase I dose-escalation study of docetaxel with granulocyte colony-stimulating factor support in patients with solid tumours. Ann Oncol 2003; 14: 788–794.[Abstract/Free Full Text]

4. Trudeau ME. Docetaxel (Taxotere): An overview of first-line monotherapy. Semin Oncol 1995; 22 (Suppl 13): 17–21.

5. Hudis CA, Seidman AD, Crown JPA et al. Phase II and pharmacologic study of docetaxel as initial chemotherapy for metastatic breast cancer. J Clin Oncol 1996; 14: 58–65.[Abstract]

6. Chan S, Friedrichs K, Noel D et al. Prospective randomized trial of docetaxel versus doxorubicin in patients with metastatic breast cancer. J Clin Oncol 1999; 17: 2341–2354.[Abstract/Free Full Text]

7. Sjostrom J, Blomqvist C, Mouridsen H et al. Docetaxel compared with sequential methotrexate and 5-fluorouracil in patients with advanced breast cancer after anthracycline failure: a randomised phase III study with crossover on progression by the Scandanavian Breast Group. Eur J Cancer 1999; 35: 1194–1201.[CrossRef][ISI][Medline]

8. Nabholtz JM, Senn HJ, Bezwoda WR et al. Prospective randomized trial of docetaxel versus mitomycin plus vinblastine in patients with metastatic breast cancer progressing despite previous anthracycline-containing chemotherapy. J Clin Oncol 1999; 17: 1413–1424.[Abstract/Free Full Text]

9. O’Shaughnessy J, Miles D, Vukelja S et al. Superior survival with capecitabine plus docetaxel combination therapy in anthracycline-pretreated patients with advanced breast cancer: phase III trial results. J Clin Oncol 2002; 20: 2812–2823.[Abstract/Free Full Text]

10. Begley CG, Basser RL, Mansfield R et al. Enhanced levels and enhanced clonogenic capacity of blood progenitor cells following administration of stem cell factor plus granulocyte colony-stimulating factor to humans. Blood 1997; 90: 3378–3389.[Abstract/Free Full Text]

11. Goss G, Grigg A. Intermediate dose cyclophosphamide combined with a growth factor is a safe and effective regimen for mobilisation of peripheral blood progenitor cells. Aust N Z J Med 1996; 26: 411–413.[ISI][Medline]

12. Knudsen LM, Gaarsdal E, Jensen L et al. Evaluation of CD34+ cell counts to guide timing and yield of large-scale collection by leukapheresis. J Hematother 1998; 7: 45–52.[ISI][Medline]

13. Smith IC, Heys SD, Hutcheon AW et al. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 2002; 20: 1456–1466.[Abstract/Free Full Text]

14. Citron ML, Berry DA, Cirrincione C et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 2003; 21: 1431–1439.[Abstract/Free Full Text]

15. Rolston KV, Berkey P, Bodey GP et al. A comparison of imipenem to ceftazidime with or without amikacin as empiric therapy in febrile neutropenia patients. Arch Intern Med 1992; 152: 283–291.[Abstract]

16. Androulakis N, Kourousis C, Dimopoulos MA et al. Treatment of pancreatic cancer with docetaxel and granulocyte colony-stimulating factor: a multicenter phase II study. J Clin Oncol 1999; 17: 1779–1785.[Abstract/Free Full Text]

17. Mavroudis D, Kourousis C, Androulakis N et al. Frontline treatment of advanced gastric cancer with docetaxel and granulocyte colony-stimulating factor (G-CSF): a phase II trial. Am J Clin Oncol 2000; 23: 341–344.[CrossRef][ISI][Medline]

18. Alexopoulos K, Kouroussis C, Androulakis N et al. Docetaxel and granulocyte colony-stimulating factor in patients with advanced non-small cell lung cancer previously treated with platinum-based chemotherapy: a multicenter phase II trial. Cancer Chemother Pharmacol 1999; 43: 257–262.[CrossRef][ISI][Medline]

19. Winer E, Berry D, Duggan D et al. Failure of higher dose paclitaxel to improve outcome in patients with metastatic breast cancer. Results from CALGB 9342. Proc Am Soc Clin Oncol 1998; 17: 101a.

20. Nabholtz JM, Gelmon K, Bontenbal M et al. Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer. J Clin Oncol 1996; 14: 1858–1867.[Abstract]

21. Eisenhauer EA, ten Bokkel Huinink WW, Swenerton KD et al. European–Canadian randomized trial of paclitaxel in relapsed ovarian cancer: high dose versus low dose and long versus short infusion. J Clin Oncol 1994; 12: 2654–2666.[Abstract]

22. Omura GA, Brady MF, Look KY et al. Phase III trial of paclitaxel at two dose levels, the higher dose accompanied by filgrastim at two dose levels in platinum-pretreated epithelial ovarian cancer: An Intergroup study. J Clin Oncol 2003; 21: 2843–2848.[Abstract/Free Full Text]

23. Bonomi P, Kim K, Fairclough D et al. Comparison of survival and quality of life in advanced non-small cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: Results of an Eastern Cooperative Oncology Group trial. J Clin Oncol 2000; 18: 623–631.[Abstract/Free Full Text]

24. Prince HM, Toner GC, Seymour JF et al. Docetaxel effectively mobilizes peripheral blood CD34+ cells. Bone Marrow Transplant 2000; 26: 483–487.[CrossRef][ISI][Medline]

25. Fleming DR, Goldsmith J, Goldsmith GH et al. Mobilization of peripheral blood stem cells in high-risk breast cancer patients using G-CSF after standard dose docetaxel. J Hematother Stem Cell Res 2000; 9: 855–860.[CrossRef][ISI][Medline]

26. Laport GG, Fleming GF, Waggoner S et al. A Phase II trial of docetaxel for peripheral blood stem cell mobilization for patients with breast cancer and ovarian cancer. Bone Marrow Transplant 2001; 27: 677–681.[CrossRef][ISI][Medline]





This Article
Abstract
Full Text (PDF)
E-letters: Submit a response
Alert me when this article is cited
Alert me when E-letters are posted
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (1)
Disclaimer
Request Permissions
Google Scholar
Articles by Mitchell, P. L. R.
Articles by Green, M.
PubMed
PubMed Citation
Articles by Mitchell, P. L. R.
Articles by Green, M.