Neoadjuvant Docetaxel Research Articles

Docetaxel as neoadjuvant therapy for radically treatablestage III non-small-cell lung cancer: a multinational randomised phase III study

Docetaxel (Taxotere) is a potent anticancer agent, with proven efficacy as first-line therapy in non-small-cell lung cancer (NSCLC). The aim of this large randomised multicentre phase III study was to evaluate docetaxel in the neoadjuvant (pre-operative) setting. Patients with stage IIIA or locally treatable IIIB NSCLC were randomly assigned to receive neoadjuvant docetaxel (n = 134) or no chemotherapy (n = 140) before surgery/curative-intention radiotherapy. Patients received up to three 3-weekly cycles of docetaxel (100 mg/m(2)) as 1-h intravenous infusions. Median survival was 14.8 months in the docetaxel group and 12.6 months in the control group. Median times to disease progression were 9.0 months (docetaxel arm) and 7.6 months (control arm). There were three complete responses and 25 partial responses in patients treated with docetaxel who were evaluable for response (n = 101). Docetaxel was well-tolerated: 103 patients (77%) received all three planned cycles. The major toxicity was grade 4 neutropenia (69 patients, 55%) and neutropenic fever (eight patients, 6%). Radiotherapy was well-tolerated after docetaxel administration. Neoadjuvant docetaxel is generally well-tolerated and shows a promising trend towards longer survival in patients with NSCLC.

Adjuvant and neoadjuvant treatments for NSCLC

In stage III non-small cell lung cancer (NSCLC), the use of induction chemotherapy prior to radiotherapy produces a significant increase in median survival of three to four months (from 11 to 14 months), a benefit which appears to be achieved through improved systemic control of the disease. Hyperfractionated radiotherapy, although it enhances local control, seems not to improve survival. Concurrent chemoradiotherapy has emerged as the most successful strategy. It led to increased locoregional control and to a 3–4 month improvement of median survival when compared with induction chemotherapy prior to radiotherapy. Docetaxel is a radiosensitizing agent and has been extensively investigated in phase I/II settings of concurrent chemoradiotherapy. Use of the other cytotoxics such as paclitaxel, or irinotecan in concurrent chemoradiotherapy strategies is also feasible. Of particular interest are the results of SWOG 9504, a phase II study in which cisplatin/etoposide concurrent chemoradiotherapy was followed by three cycles of docetaxel consolidation. Median survival is 26 months, 1-year survival 76% and 3-year survival 40%. These survival data, achieved in pathologically staged IIIB patients, are highly encouraging and support further evaluation of this approach. Among stage III patients eligible for radical treatment with surgery or radiotherapy, the addition of neoadjuvant docetaxel at 100 mg/m 2 for three cycles is tolerable and appears to be associated with a trend towards increased survival.

Neoadjuvant Docetaxel in Breast Cancer: 3-Year Survival Results from the Aberdeen Trial

Over the past 30 years there has been an increased use of neoadjuvant (or primary) chemotherapy for treating patients with breast cancer. However, while it is clear that chemotherapy given in the adjuvant setting after surgery does prolong patients' overall and disease-free survival, the evidence that chemotherapy in the neoadjuvant setting also increases survival remains unproven. In the Aberdeen study, 162 patients with large and locally advanced breast cancer underwent 4 cycles of CVAP (cyclophosphamide/vincristine/doxorubicin/prednisone) primary chemotherapy. Patients with a complete or partial response were then randomized to either 4 further cycles of CVAP or 4 cycles of docetaxel (100 mg/m 2). It was shown that the addition of sequential docetaxel (100 mg/m 2) to CVAP neoadjuvant chemotherapy resulted in a significantly enhanced clinical response rate (94% vs. 64%) and a substantially increased complete histopathological response rate (34% vs. 16%) when compared to patients receiving CVAP alone. Furthermore, patients receiving docetaxel had an increased breast conservation rate (67% vs. 48%) and an increased survival at a median follow-up of 3 years. It is important to note that this was a small study, and the survival results should be interpreted with caution. The results are encouraging, however, and further studies are urgently required.

Neo-adjuvant therapy with dose-dense docetaxel plus short-term filgrastim rescue for locally advanced breast cancer.

Neo-adjuvant, dose-dense docetaxel, 100 mg/m(2) every 2 weeks x 4 cycles, was administered to 12 patients with locally advance breast cancer (LABC) (10 stage IIIa and three stage IIIb). Eligibility requirements included a PS 0-2, normal hepatic and renal function, and radiologic absence of metastatic disease. Filgrastim [granulocyte colony stimulating factor (G-CSF)] was started 1 day after chemotherapy and was given for 6 days. Complete blood counts were determined weekly. Surgery was planned upon recovery from the last dose of docetaxel and followed by 4 cycles of adjuvant doxorubicin plus cyclophosphamide (AC) and radiotherapy. Patients with ER status received tamoxifen. The median age was 45 (range 34-73) and pre-treatment pathology revealed poorly differentiated infiltrating duct carcinoma in 11 and infiltrating lobular cancer in one, with positive ER/PR status in five. Twelve patients were treated, and all are evaluable for response and toxicity. Nine patients had a major clinical tumor response with five PR and four pathologic complete responses (pCR rate of 33%). Three patients (of whom two with stage IIIb) had progressive disease and went on to receive neo-adjuvant therapy with AC. There was one instance of grade 3 hematologic toxicity (neutropenic fever in one G-CSF non-compliant patient). There were two instances of grade 3 extra-hematologic toxicity: one patient had severe pain and one had treatment-related fatigue. After a median follow-up of 20 months (range 7-49 months) all patients are alive and eight of nine responders remain progression-free. Despite the small size of our study, we believe that dose-dense neo-adjuvant docetaxel is well tolerated and its activity warrants confirmation in a larger number of patients.

Neoadjuvant Docetaxel Augments the Efficacy of Preoperative Doxorubicin/Cyclophosphamide in Operable Breast Cancer: First Results of NSABP B-27

Neoadjuvant Docetaxel Augments the Efficacy of Preoperative Doxorubicin/Cyclophosphamide in Operable Breast Cancer: First Results of NSABP B-27

Neoadjuvant Chemotherapy in Breast Cancer: Significantly Enhanced Response With Docetaxel

To compare the efficacy of neoadjuvant (NA) docetaxel (DOC) with anthracycline-based therapy and determine the efficacy of NA DOC in patients with breast cancer initially failing to respond to anthracycline-based NA chemotherapy (CT). Patients with large or locally advanced breast cancer received four pulses of cyclophosphamide 1,000 mg/m(2), doxorubicin 50 mg/m(2), vincristine 1.5 mg/m(2), and prednisolone 40 mg (4 x CVAP) for 5 days. Clinical tumor response was assessed. Those who responded (complete response [CR] or partial response [PR]) were randomized to receive further 4 x CVAP or 4 x DOC (100 mg/m(2)). All nonresponders received 4 x DOC. One hundred sixty-two patients were enrolled; 145 patients completed eight cycles of NA CT. One hundred two patients (66%) achieved a clinical response (PR or CR) after 4 x CVAP. After randomization, 50 patients received 4 x CVAP and 47 patients received 4 x DOC. In patients who received eight cycles of CT, the clinical CR (cCR) and clinical PR (cPR) (94% v 66%) and pathologic CR (pCR) (34% v 16%) response rates were higher (P =.001 and P =.04) in those who received further DOC. Intention-to-treat analysis demonstrated cCR and cPR (85% v 64%; P =.03) and pCR (31% v 15%; P =.06). Axillary lymph node examination revealed residual tumor in 33% of patients who received 8 x CVAP and 38% of patients who received further DOC. In patients who failed to respond to the initial CVAP, 4 x DOC resulted in a cCR and cPR rate of 55% and a pCR rate of 2%. Forty-four percent of these patients had residual tumor within axillary lymph nodes. NA DOC resulted in substantial improvement in responses to DOC.

Neoadjuvant Chemotherapy in Breast Cancer: Significantly Enhanced Response With Docetaxel

PURPOSE: To compare the efficacy of neoadjuvant (NA) docetaxel (DOC) with anthracycline-based therapy and determine the efficacy of NA DOC in patients with breast cancer initially failing to respond to anthracycline-based NA chemotherapy (CT). PATIENTS AND METHODS: Patients with large or locally advanced breast cancer received four pulses of cyclophosphamide 1,000 mg/m2, doxorubicin 50 mg/m2, vincristine 1.5 mg/m2, and prednisolone 40 mg (4 × CVAP) for 5 days. Clinical tumor response was assessed. Those who responded (complete response [CR] or partial response [PR]) were randomized to receive further 4 × CVAP or 4 × DOC (100 mg/m2). All nonresponders received 4 × DOC. RESULTS: One hundred sixty-two patients were enrolled; 145 patients completed eight cycles of NA CT. One hundred two patients (66%) achieved a clinical response (PR or CR) after 4 × CVAP. After randomization, 50 patients received 4 × CVAP and 47 patients received 4 × DOC. In patients who received eight cycles of CT, the clinical CR (cCR) and clinical PR (cPR) (94% v 66%) and pathologic CR (pCR) (34% v 16%) response rates were higher (P = .001 and P = .04) in those who received further DOC. Intention-to-treat analysis demonstrated cCR and cPR (85% v 64%; P = .03) and pCR (31% v 15%; P = .06). Axillary lymph node examination revealed residual tumor in 33% of patients who received 8 × CVAP and 38% of patients who received further DOC. In patients who failed to respond to the initial CVAP, 4 × DOC resulted in a cCR and cPR rate of 55% and a pCR rate of 2%. Forty-four percent of these patients had residual tumor within axillary lymph nodes. CONCLUSION: NA DOC resulted in substantial improvement in responses to DOC.

Promising clinical and pathological response rates with neoadjuvant sequential doxorubicine (DOX) and docetaxel (DOC) in locally advanced breast cancer (LABC)

Promising clinical and pathological response rates with neoadjuvant sequential doxorubicine (DOX) and docetaxel (DOC) in locally advanced breast cancer (LABC)

Neoadjuvant Docetaxel Augments the Efficacy of Preoperative Docetaxel/Cyclophosphamide in Operable Breast Cancer: First Results of NSABP B-27

py was initially reserved for patients with locally advanced breast cancer who could not be offered standard surgical interventions, such as those with inoperable locally advanced disease. However, there are several reasons to consider the use of neoadjuvant treatment for patients with operable breast cancer as well. First, neoadjuvant chemotherapy may be useful in reducing tumor size, thereby allowing a higher rate of breast conserving surgery. Second, neoadjuvant therapy allows for earlier treatment of micrometastases. Third, neoadjuvant chemotherapy serves as an in vivo chemosensitivity assay, identifying at an early time point those patients who may be refractory to standard regimens and who may need to explore alternative therapies. Finally, neoadjuvant therapy has been shown to improve local control and disease-free overall survival (DFS) 1,2 in patients with locally advanced or inflammatory breast cancer and similar results may occur in patients with early-stage breast cancer as well. The potential disadvantage to neoadjuvant chemotherapy is a delay in local therapy.

Neoadjuvant docetaxel followed by radical prostatectomy in patients with high-risk localized prostate cancer: A preliminary report

Neoadjuvant docetaxel followed by radical prostatectomy in patients with high-risk localized prostate cancer: A preliminary report

Neoadjuvant docetaxel followed by radical prostatectomy in patients with high-risk localized prostate cancer: A preliminary report

Effective treatment options for high-risk localized prostate cancer are limited. Patients at high risk for recurrence include those with biopsy Gleason scores of 8 to 10, prostate specific antigen (PSA) levels > 20 ng/mL, and clinical stage T3 disease. Docetaxel chemotherapy is active in hormone-refractory prostate cancer, either combined with estramustine or used as a single agent. To determine if systemic therapy can improve the out-come of radical prostatectomy in men with high-risk localized prostate cancer, we are undertaking a pilot phase II clinical trial of weekly docetaxel at 36 mg/m 2 for up to 6 months, followed by surgery. Patients are monitored with weekly visits, monthly digital rectal examinations, PSA measurement, and testosterone tests, and endorectal magnetic resonance imaging done at baseline, after two cycles, and again after six cycles. To date, 15 patients have been enrolled, and 70 cycles of chemotherapy have been administered. Toxicity has been mostly grade 1 in intensity, and fatigue has been the most common grade 2 toxicity reported. The primary endpoint of the trial is measurement of pathologic complete response rate, for which data are not yet available. Recruitment to the trial is ongoing.

Preliminary observations of single-agent docetaxel as neoadjuvant therapy for locally advanced prostate cancer

Patients with locally advanced prostate cancer present a significant therapeutic dilemma. Despite aggressive local therapies, including radical prostatectomy (RP), these patients are at high risk for biochemical failure. Several research groups have recently demonstrated the feasibility of hormonal and chemohormonal therapy before RP, but limited published data are available regarding the usefulness of chemotherapy without hormonal therapy in the neoadjuvant setting. At Cleveland Clinic Foundation, a phase II trial was initiated to evaluate a 6-week course of docetaxel, 40 mg/m 2 intravenously every 7 days, followed by RP in patients with locally advanced prostate cancer. RP was to be performed within 3 weeks of completion of neoadjuvant chemotherapy. The primary endpoint of this study is pathologic complete response. Preliminary toxicity data suggest that weekly docetaxel is well tolerated and does not increase the risk of perioperative or post-operative complications. Reductions in prostate-specific antigen levels were noted in seven of 10 patients who completed the 6-week course of neoadjuvant docetaxel. The neoadjuvant use of investigational cancer therapies may allow for relatively rapid assessment of their antitumor activity.

Neoadjuvant chemotherapy with docetaxel in non-small cell lung cancer

Based on proven activity and survival benefit in advanced non-small cell lung cancer, docetaxel has been introduced into neoadjuvant therapy. In a large, phase III randomized trial in 274 stage IIIA and IIIB patients, treatment with an induction regimen of 100 mg/m 2 docetaxel for three cycles before definitive surgery or radiotherapy was associated with an encouraging trend towards longer median survival. Overall 1-year survival was 59% compared with 51% in the control group. Docetaxel in the neoadjuvant setting was well tolerated and did not compromise later radical local therapy. The incidence of grade 3 4 esophagitis, for example, was less than 1% in patients who had had induction docetaxel followed by curative radiotherapy. This also was true for pneumonitis. Neoadjuvant docetaxel in combination with cisplatin or carboplatin is being evaluated in phase II trials which have reported response rates of 66% to 82% and rates of complete resection ranging from 69% to 79%. Docetaxel also is being investigated in combination with both cisplatin and gemcitabine in phase I/II studies. Phase III trials will further define the promising role of docetaxel alone and in combination in neoadjuvant therapy.

Docetaxel: a review of its use in non-small cell lung cancer.

Docetaxel, a semisynthetic member of the taxoid class of antineoplastic agents, is effective in the treatment of patients with locally advanced and metastatic non-small cell lung cancer (NSCLC). In noncomparative trials in patients with NSCLC, docetaxel 75 or 100 mg/m2 produced objective response rates of 20 to 38% and 14 to 25% as a first-line or second-line monotherapy, respectively. In Japan, docetaxel 60 mg/m2 produced objective response rates of 19 to 25% in previously untreated patients. Docetaxel 100 or 75 mg/m2 produced significantly higher response rates than either vinorelbine or ifosfamide in previously treated patients; patients treated with docetaxel 75 mg/m2 had an improved 1-year survival rate compared with those who received vinorelbine or ifosfamide. Docetaxel monotherapy in chemotherapy-naive patients produced survival rates that are similar to those reported for most platinum-containing standard combinations such as cisplatin plus vinorelbine. Combination of docetaxel with one other antineoplastic resulted in objective response rates of 20 to 54% in chemotherapy-naive patients; triple chemotherapy combinations produced responses in 51 and 60% of patients. Promising results from a few small studies and one large phase II study have also indicated a potential role for docetaxel as neoadjuvant therapy. The main dose-limiting adverse event associated with docetaxel is neutropenia, and fluid retention is common in many patients. The tolerability profile is generally acceptable in the majority of patients, although extra care has to be taken in patients with impaired liver function to minimise the risk of severe or febrile neutropenia. Conclusions. Docetaxel is generally well tolerated by patients receiving treatment for locally advanced and metastatic NSCLC, and produces response and survival rates equivalent to many current standard treatment options. Comparative studies have shown that docetaxel monotherapy provides significant survival benefits over best supportive care or treatment with vinorelbine or ifosfamide. Response and 1-year survival rates with docetaxel monotherapy are particularly encouraging in patients refractory or resistant to cisplatin or carboplatin, for whom treatment options are few. Neoadjuvant docetaxel has produced improved survival compared with local treatment alone. Combinations of docetaxel with other antineoplastic agents have produced relatively high response and 1-year survival rates; however, further comparative studies are required to confirm these benefits. In the meantime, docetaxel is a welcome addition to the options available for patients with advanced NSCLC.