Neoadjuvant Docetaxel Research Articles

Phase II trial of neoadjuvant docetaxel and gefitinib followed by radical prostatectomy in patients with high‐risk, locally advanced prostate cancer

Prostate cancer trials investigating neoadjuvant hormonal therapy, followed by surgery, have demonstrated that elimination of all tumor cells from the primary site is rare. The authors report a phase 2 trial assessing the efficacy and toxicity of docetaxel and gefitinib in patients with high-risk localized prostate cancer as neoadjuvant therapy before radical prostatectomy (RP). Thirty-one patients with high-risk prostate cancer were treated with docetaxel and gefitinib for 2 months before RP. All patients met the criteria of clinical stage T2b-3 or serum prostate-specific antigen (PSA) level >20 ng/mL, or Gleason score of 8 to 10. The primary endpoint was pathologic complete response. Secondary objectives included clinical response. When available, endorectal coil magnetic resonance imaging (eMRI) was performed as part of clinical response evaluation. Immunohistochemical staining of epidermal growth factor receptor and HER-2/neu was performed on prechemotherapy and postchemotherapy prostate tissue. The median age of the patients was 60 years, the median pretreatment PSA level was 7.43 ng/mL, and the median Gleason score was 8. Clinical staging prior to treatment consisted of: T1 in 4 patients, T2 in 17 patients, and T3 in 10 patients. One patient with enlarged pelvic adenopathy and T4 disease did not undergo RP. Thirty patients received all scheduled therapies including RP. Grade 3 toxicities included asymptomatic liver function test elevation in 4 (13%) patients, diarrhea in 1 (3%) patient, and fatigue in 1 (3%) patient. One patient experienced grade 4 toxicity with elevated alanine aminotransferase. RP specimen pathology demonstrated residual carcinoma in all cases. Twenty-nine (94%) patients achieved a clinical partial response, including 35% of patients who demonstrated radiographic improvement on eMRI. No pathologic complete response was noted in 31 patients treated with docetaxel and gefitinib. This combination was well tolerated, and did not result in increased surgical morbidity.

Randomized Phase II Trial of Concurrent Cisplatin-Radiotherapy With or Without Neoadjuvant Docetaxel and Cisplatin in Advanced Nasopharyngeal Carcinoma

To compare the toxicities, tumor control, survival, and quality of life of nasopharyngeal cancer (NPC) patients treated with sequential neoadjuvant chemotherapy followed by concurrent cisplatin-radiotherapy (CRT) or CRT alone. Previously untreated stage III to IVB NPC were randomly assigned to (1) neoadjuvant docetaxel 75 mg/m(2) and cisplatin 75 mg/m(2) every 3 weeks for two cycles, followed by cisplatin 40 mg/m(2)/wk concurrent with radiotherapy, or (2) CRT alone. Planned accrual was 30 patients per arm to detect 20% difference of toxicities based on 95% CIs. From November 2002 to November 2004, 65 eligible patients were randomly assigned to neoadjuvant chemotherapy followed by CRT (n = 34) or CRT alone (n = 31). There was a high rate of grade 3/4 neutropenia (97%) but not neutropenic fever (12%) during neoadjuvant chemotherapy. No significant differences in rates of acute toxicities were observed between the two arms during CRT. Dose intensities of concurrent cisplatin, late RT toxicities and quality of life scores were comparable in both arms. The 3-year progression-free survival for neoadjuvant versus control arm was 88.2% and 59.5% (hazard ratio = 0.49; 95% CI, 0.20 to 1.19; P = .12). The 3-year overall survival for neoadjuvant versus control arm was 94.1% and 67.7% (hazard ratio = 0.24; 95% CI, 0.078 to 0.73; P = .012). Neoadjuvant docetaxel-cisplatin followed by CRT was well tolerated with a manageable toxicity profile that allowed subsequent delivery of full-dose CRT. Preliminary results suggested a positive impact on survival. A phase III study to definitively test this neoadjuvant-concurrent strategy is warranted.

Neoadjuvant Platelet Derived Growth Factor Receptor Inhibitor Therapy Combined With Docetaxel and Androgen Ablation for High Risk Localized Prostate Cancer

Platelet derived growth factor receptor inhibitor therapy improves the efficacy of taxane chemotherapy in preclinical models of prostate cancer. Men with high risk localized prostate cancer were treated with platelet derived growth factor receptor inhibitor therapy, docetaxel and hormone ablation in the preoperative setting, and clinicopathological outcomes were evaluated. A total of 36 men with cT2 or greater disease, Gleason grade 8-10, serum prostate specific antigen more than 20 ng/ml or cT2b and prostate specific antigen more than 10 ng/ml and Gleason 7 disease, without radiological evidence of metastases, were scheduled to receive intramuscular leuprolide, 600 mg daily oral imatinib and 30 mg/m(2) weekly docetaxel x 4 every 42 days for 3 cycles before radical prostatectomy (beta [0.02, 1.98] prior on the possibility of pathological complete remission). Unresectable disease, postoperative prostate specific antigen 0.2 ng/ml or greater, or administration of postoperative radiation or hormones were defined as treatment failure. A total of 39 men were registered over 15 months. Median patient age was 57 years (range 44 to 71). Risk factors included T3 disease (22 of 39), Gleason 8-10 disease (31 of 39) and prostate specific antigen more than 20 ng/ml (12 of 39). Three men were ineligible or declined therapy, 29 of 36 (81%) received 3 cycles of therapy and 7 of 36 (19%) discontinued therapy related to toxicity. Grades 3-4 toxicity included rash (4), diarrhea (4), fatigue (6) and neutropenia (1). The surgical approach was feasible, without excessive or unusual complications such as wound dehiscence. No pathological complete remissions were defined. At a median followup of 39 months 53% were free from progression. Evidence for a favorable impact of platelet derived growth factor receptor inhibitor therapy on the efficacy of neoadjuvant docetaxel and hormonal ablation in high risk localized prostate cancer was not obtained.

Clusterin knockdown using the antisense oligonucleotide OGX‐011 re‐sensitizes docetaxel‐refractory prostate cancer PC‐3 cells to chemotherapy

To characterize changes in secretory clusterin (sCLU) expression in prostate cancer cells after treatment with docetaxel and to determine whether sCLU knockdown can re-introduce chemosensitivity in a docetaxel-resistant, androgen-independent human prostate cancer model. A tissue microarray was constructed for 84 radical prostatectomy (RP) specimens from a multicentre Phase II trial of neoadjuvant combined androgen ablation and docetaxel (CUOG-P01a) and assessed for changes in the expression of the cytoprotective chaperone sCLU. The human prostate cancer cell line PC-3 was repeatedly exposed to docetaxel chemotherapy in vitro, and a docetaxel-resistant cell subline (PC-3dR) was developed and analysed. sCLU levels were significantly higher in RP specimens treated with neoadjuvant combined androgen ablation and docetaxel than in untreated specimens. Similarly, sCLU expression increased 2.5-fold in the newly developed docetaxel-refractory PC-3dR cell line compared with parental PC-3 cells. There was a dose-dependent and sequence-specific decrease in sCLU levels in PC-3dR cells using OGX-011, an antisense oligonucleotide against human sCLU. OGX-011 and small-interference RNA both chemosensitized PC-3dR cells to docetaxel and mitoxantrone in vitro and apoptotic rates in PC-3dR cells were significantly increased when OGX-011 was combined with docetaxel. In vivo, growth of PC-3dR xenografts in nude mice was synergistically inhibited by OGX-011 combined with paclitaxel or mitoxantrone (by 76% and 44% compared with their mismatch controls, respectively). The present findings indicate that targeted knockdown of sCLU enhances the effects of cytotoxic chemotherapy in docetaxel-refractory cells, and provide preclinical proof of principle for clinical trials testing OGX-011 in second-line chemotherapy regimens for patients with docetaxel-refractory prostate cancer.

Multicenter Phase II Study of Combined Neoadjuvant Docetaxel and Hormone Therapy Before Radical Prostatectomy for Patients With High Risk Localized Prostate Cancer

We assessed pathological outcomes as well as the feasibility of combined docetaxel and androgen deprivation therapy in men with prostate cancer before undergoing prostatectomy. In this phase II multicenter study of newly diagnosed patients with untreated clinically localized prostate cancer and high risk features, all patients received androgen deprivation therapy (6.3 mg buserelin acetate every 8 weeks for 3 doses and antiandrogen for 4 weeks) with docetaxel (35 mg/m(2) weekly for 6 of 8 weeks for 3 doses). A total of 72 men with a median age of 59 years (range 46 to 78) were enrolled in the study. Baseline characteristics included clinical stage T1C, T2 or T3 in 14%, 47% and 39%, and Gleason score 7 or less, 8 and 9 in 40%, 29% and 31% of patients, respectively. Median baseline prostate specific antigen was 10.8 mug/l (range 1.6 to 65.6). Eight patients did not complete protocol therapy because of toxicity (4), withdrawal of consent (1) and other reasons (3). Of the 64 patients completing protocol therapy 2 had a complete pathological response. Pathological stage was T2 in 53% and T3 in 44% of patients. Four patients had N1 disease and positive surgical margins were identified in 27%. At a median followup of 42.7 months (range 25.6 to 65.6) 19 patients (30%) had disease relapse. Combined androgen deprivation and docetaxel before prostatectomy was feasible, and resulted in encouraging recurrence-free survival. While pathological down staging was observed, pathological complete response rates were rare.

Pediatric and young adult (

21003 Background: Evaluate treatment results of the pediatric and young adult (< 21 year of age) patients with non-metastatic nasopharyngeal carcinoma (NPC) who were treated with neoadjuvant cisplatin + docetaxel (CD) and radiotherapy. Patients and Methods: Ten patients with NPC diagnosed between 2004–2007 have been treated with four cycles of CDDP 100 mgr/m2 + docetaxel 75 mg/m2 on day 1 with premedication every three weeks. Radiotherapy doses were 60 Gy to the primary tumor and positive lymph node regions and 40 Gy supraclavicular field by shielding the clavicules. Five children was monitored with serum EBV DNA quantification at diagnosis, after each cycle of chemotherapy, before radiotherapy and at follow-up. Results: Median age of the patients was 14 (9–20) with a male/female ratio of 6/4. Stage distribution was as follows: 2 with stage IIb, 2 with stage III, 4 pts with stage IVa, and 2 with stage IVb. One patient had a near complete response, 5 had partial response, and 3 had stable disease after CD chemotherapy and 1 progressed during CD chemotherapy. Over all survival rate in our protocol was 90%, whereas event free survival rate was 80%. No major chemotherapy toxicity was observed. EBV DNA titers were higher levels in two out of five patients at the time of diagnosis. Conclusion: Cisplatin+docetaxel combination was safe and effective in childhood nasopharyngeal carcinoma. There were no major toxicity during the chemotherapy. Plasma EBV DNA is useful for monitoring patients with nasopharyngeal carcinoma and predicting the outcome of treatment. No significant financial relationships to disclose.

Efficacy of neoadjuvant bevacizumab (Av), capecitabine (X), and docetaxel (T) for invasive breast cancer (BC): Phase II result

14575 Background: In metastatic BC, Av significantly improves patient (pt) outcomes when added to paclitaxel and has been evaluated in a large, phase III trial in combination with T (AVADO). Adding X to T significantly improves overall survival and the XTAv triplet combination is highly active first-line for metastatic BC. To evaluate XTAv in early BC, we initiated a pilot, phase II study in pts scheduled to receive neoadjuvant chemotherapy. Methods: Pts with invasive HER2-negative T2–4c >2 cm, N0–3, M0 BC and no prior systemic therapy received 21-day cycles of Av 15 mg/kg (30–90-minute IV infusion, d1×5 cycles) plus T 75 mg/m2 (d1×6 cycles) plus X (950 mg/m2 bid 14d on/7d off×6 cycles). Pts underwent surgery 2–4 weeks after completing XTAv, followed by radiotherapy, chemotherapy, and hormone therapy according to institution guidelines. Pathologic complete response (pCR), the primary endpoint, was defined as no evidence of invasive tumor in the final surgical sample (T0 or DCIS). Secondary endpoints included clinical response rate (RR), breast-conserving surgery (BCS) rate, and safety. Results: Baseline characteristics (n=18) were: median age 48 years (range 34–69); T4a (6%), T3 (39%), T2 (56%); ER+ (67%); PR+ (61%). Most pts (72%) received all 6 cycles. BCS was possible in 14 pts (78%; 95% CI: 52–94); 2 additional pts (11%) had BCS followed later by mastectomy and 2 pts (11%) underwent modified radical mastectomy. Sentinel lymph nodes were negative in 10 (67%) of 15 pts undergoing sentinel biopsy. pCR rate was 22% (95% CI: 6–48). Clinical RR was 83%. T stage was T3 (17%), T2 (11%), T1 (50%), CIS (6%), T0 (17%). XTAv was well tolerated, with no unexpected toxicities. Conclusions: The 22% pCR rate suggests that the activity of XT in HER2-negative BC can be increased by adding Av. Further evaluation of this regimen in early BC is recommended. No significant financial relationships to disclose.

Phase II trial of neoadjuvant docetaxel (T), cisplatin (P), and cetuximab (E) followed by concurrent radiation (X), P, and E in locally advanced head and neck cancer (HNC)

6002 Background: We incorporated E, a chimeric IgG1 monoclonal antibody against the epidermal growth factor receptor, into the induction therapy and subsequent chemoradiotherapy of HNC. Methods: Patients (pts) had previously untreated, stage III/IV squamous cell or undifferentiated carcinoma of the HN, ECOG PS 0–1, and adequate laboratory parameters. Induction consisted of T 75 mg/m² day 1, P 75 mg/m² day 1, and E 250 mg/m² days 1,8, and 15 (after an initial dose of 400 mg/m² on cycle 1, day 1), repeated every 21 days x 3 cycles, with prophylactic antibiotics. Subsequently, pts received 70 Gy (2 Gy/day) with concurrent P 30 mg/m² and E 250 mg/m² weekly, followed by maintenance E for 6 months. Sample size was 39 pts; target overall response rate (ORR) to TPE: 80%. Results: From 1/06 to 10/07, 39 pts were enrolled: median age 52 (21–74); male: 34; stage IV: 35; primary site: oropharynx, 23; larynx, 5; hypopharynx, 3, oral cavity, 3; nasopharynx, 3; and unknown, 2. 36 pts received all 3 cycles of TPE (2 pts discontinued treatment due to infusion reactions and 1 due to complications); 34 pts received XPE with median of 7 weekly P doses; 2 pts were switched to carboplatin. In 37 pts evaluable for response using RECIST, the ORR to TPE was 32/37 (86%); CR 2, PR 30, SD 5; in the primary, 19/26 (73%) had CR by clinical exam and 13/22 (59%) by PET. After XPE (n=28), the ORR was 100%; CR 8, PR 20; in the primary, 22/22 (100%) had CR by exam and 19/22 (86%) by PET. 3 pts underwent neck dissection for presumed residual disease; 2/3 had pCR. With a median follow-up of 12 months (3–23), 4 pts progressed (3 local, 1 distant); 1 pt had salvage surgery and remains disease free. 4 pts died (1 due to myocardial infarction and 3 of disease progression). Serious toxicities during TPE included grade (G) 3/4 neutropenia, 8/20; neutropenic fever, 4; G 3 infection, 3; G 3 anemia, 2; G 3 thrombocytopenia, 1; G 3/4 hypomagnesemia, 3/1; G 3 rash, 1; G 3 mucositis, 1; G 3 diarrhea, 2. During XPE (n=30): G 3 mucositis, 15; G 3/4 dermatitis, 8/1; G 3/4 hypomagnesemia, 5/6; G 3 infection, 7; neutropenic fever, 2. Conclusions: TPE followed by XPE has manageable toxicities and substantial activity in HNC. Early survival results are promising. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Bristol-Myers Squibb

Sequential addition of a semi-intensive anthracycline-based regimen (TNCF) to docetaxel as neoadjuvant treatment of operable breast cancer: An update at five years

11516 Background: To update the results of a phase II combining sequentially neoadjuvant docetaxel to a semi-intensive anthracycline-based regimen (TNCF); to compare these results to those of a larger 710 patients database in which patients were treated between 1982 and 2004 by several neoadjuvant chemotherapy protocols. Methods: From 2001 through 2003, 53 patients received four cycles of docetaxel, followed by a maximum of four cycles of TNCF every 21 days (Amat et al, Clin Breast Cancer, 2006). On completion of chemotherapy, patients underwent surgery and radiotherapy, then adjuvant treatment. Forty-four tumors (83%) were stage II disease (18 stage IIA and 26 stage IIB) and 9 (17%) were stage IIIa disease. In all, 43 (81%) patients had a canalar and 4 (7.5%) a lobular invasive carcinoma. 30% of the tumours were grade III SBR and 64% had at least one-positive HR. Patients received up to 8 cycles (median: 6 [range, 4–8]) ea. 21 days. Results: Clinical objective response rate (ORR) was 79% [CI 95% : 68–90]...

Preferential pathologic complete response (pCR) by triple-negative (-) breast cancer to neoadjuvant docetaxel (T) and carboplatin (C)

604 Background: Breast cancer is heterogeneous with subtypes having distinct biologies and clinical outcomes. This study determined whether pCR of breast cancer to 4 cycles of neoadjuvant T/C is af...

Neoadjuvant docetaxel plus adriamycin combination chemotherapy in patients with inflammatory breast cancer – a single institution experience

To review the potential contributory role of biofilms to post-tympanstomy tube otorrhea and plugging as well as the available interventions currently utilized to prevent biofilm formation on tympanostomy tubes.A literature review was performed utilizing the MEDLINE/Pubmed database from 1980 to 2013.Electronic database was searched with combinations of keywords “biofilm”, “tympanostomy tube”, “ventilation tube”, and “post-tympanostomy tube otorrhea”.Two of the most common sequelae that occur after tympanostomy tube insertion are otorrhea and tube occlusion. There is an increased evidence supporting a role for biofilms in the pathogenesis of otitis media. In this review, we have shown a multitude of novel approaches for prevention of biofilm associated sequelae of otitis media with effusion. These interventions include (i) changing the inherent composition of the tube itself, (ii) coating the tubes with antibiotics, polymers, plant extracts, or other biofilm-resistant materials, (iii) tubal impregnation with antimicrobial compounds, and (iv) surface alterations of the tube by ion-bombardment or surface ionization.Currently, there is not one type of tympanostomy tube in which bacteria will not adhere. The challenges of treating chronic post-tympanostomy tube otorrhea and tube occlusion indicate the need for further research in optimization of tympanostomy tube design in addition to development of novel therapies.

Neoadjuvant docetaxel (DOC 75) followed by fluorouracil, epirubicin, cyclophosphamide (FEC 100) in primary operable breast cancer: results of a multicenter phase II trial

Neoadjuvant docetaxel (DOC 75) followed by fluorouracil, epirubicin, cyclophosphamide (FEC 100) in primary operable breast cancer: results of a multicenter phase II trial

Neoadjuvant Docetaxel and Capecitabine in Patients With High Risk Prostate Cancer

Docetaxel is the most active cytotoxic agent in hormone refractory prostate cancer. Preclinically docetaxel increases expression of thymidine phosphorylase, an enzyme responsible for activation of capecitabine to 5-fluorouracil resulting in increased antitumor activity. We assessed activity and safety of neoadjuvant docetaxel and capecitabine in patients with high risk prostate cancer. Patients with either clinical stage greater than T2, prostate specific antigen 15 ng/ml or more, or Gleason sum 8 or greater received 3 to 6 cycles of docetaxel (36 mg/m2 intravenously on days 1, 8 and 15) and capecitabine (1,250 mg/m2 per day orally divided twice a day on days 5 to 18) every 28 days, followed by local therapy. The primary end point was rate of 50% or greater prostate specific antigen decrease. Correlative studies included qualitative changes in histology, tissue thymidine phosphorylase and survivin expression, and CK18Asp396 (serum apoptosis marker). A total of 15 patients were treated, of whom 6 (40%) experienced a 50% or greater decrease in prostate specific antigen with infrequent diarrhea or hand-foot syndrome. Eleven patients underwent radical prostatectomy. There were no pathological complete responses and 4 patients demonstrated mild histological changes, including focal necrosis and vacuolated cytoplasm. While there was no discernable pattern of increased thymidine phosphorylase expression, 4 specimens showed decreased survivin expression, suggesting a possible mechanism for chemotherapy induced apoptosis. There was no correlation of prostate specific antigen response and survivin expression, and no increase in serum CK18Asp396. Neoadjuvant docetaxel and capecitabine is well tolerated but is not associated with significant pathological and prostate specific antigen responses.

Prognostic impact of clinicopathologic parameters in stage II/III breast cancer treated with neoadjuvant docetaxel and doxorubicin chemotherapy: paradoxical features of the triple negative breast cancer

BackgroundPrognostic factors in locally advanced breast cancer treated with neoadjuvant chemotherapy differ from those of early breast cancer. The purpose of this study was to identify the clinical significance of potential predictive and prognostic factors in breast cancer patients treated by neoadjuvant chemotherapy.MethodsA total of 145 stage II and III breast cancer patients received neoadjuvant docetaxel/doxorubicin chemotherapy were enrolled in this study. We examined the clinical and biological factors (ER, PR, p53, c-erbB2, bcl-2, and Ki-67) by immunohistochemistry. We analyzed clinical outcome and their correlation with clinicopathologic parameters.ResultsAmong the clinicopathologic parameters investigated, none of the marker was correlated with response rate (RR) except triple negative phenotype. Patients with triple negative phenotype showed higher RR (83.0% in triple negative vs. 62.2% in non-triple negative, p = 0.012) and pathologic complete RR (17.0% in triple negative vs. 3.1% in non-triple negative, p = 0.005). However, relapse free survival (RFS) and overall survival (OS) were significantly shorter in triple negative breast cancer patients (p < 0.001, p = 0.021, respectively). Low histologic grade, positive hormone receptors, positive bcl-2 and low level of Ki-67 were associated with prolonged RFS. In addition, positive ER and positive bcl-2 were associated with prolonged OS. In our homogeneous patient population, initial clinical stage reflects RFS and OS more precisely than pathologic stage. In multivariate analysis, initial clinical stage was the only significant independent prognostic factor to impact on OS (hazard ratio 3.597, p = 0.044).ConclusionSeveral molecular markers provided useful predictive and prognostic information in stage II and III breast cancer patients treated with neoadjuvant docetaxel/doxorubicin chemotherapy. Triple negative phenotype was associated with shorter survival, even though it was associated with a higher response rate to neoadjuvant chemotherapy.

Neoadjuvant docetaxel and cisplatin chemotherapy followed by local irradiation is highly active on locoregionally advanced squamous cell carcinoma of the head and neck

The purpose of this study was to determine the treatment outcome of neoadjuvant docetaxel and cisplatin chemotherapy followed by local radiotherapy for chemotherapy-naïve patients with locoregionally advanced squamous cell carcinoma of the head and neck. Thirty-seven patients with stage III or IV squamous cell carcinoma of the head and neck who received docetaxel and cisplatin regimen for a maximum of three cycles followed by radiation therapy were enrolled in this study. The overall response rate to the regimen was 91.9 per cent (34 of 37) (the complete remission rate was 48.6 per cent). The median time to treatment failure was 38 months (95 per cent confidence interval, 15-61 months). The four year estimated overall survival rates were 85.1 per cent. The most frequent moderate-to-severe toxicity was grade 3-4 neutropenia. The most common acute non-haematologic toxicities included anorexia, nausea and asthenia. Neoadjuvant docetaxel and cisplatin chemotherapy followed by radiotherapy is a feasible treatment strategy for patients with locoregionally advanced squamous cell carcinoma of the head and neck.

2060 POSTER An open-label study of neoadjuvant capecitabine (C) and docetaxel (D) with/without trastuzumab (T) to determine the role of p53 mutations in clinical and pathological responses in patients with recently diagnosed breast cancer (BC)

To compare partial-breast clinical target volumes generated using a standard 15 mm margin (CTVstandard) with those generated using three-dimensional surgical excision margins (CTVtailored30) in women who have undergone wide local excision (WLE) for breast cancer.Thirty-five women underwent WLE with placement of clips in the anterior, deep and coronal excision cavity walls. Distances from tumour to each of six margins were measured microscopically. Tumour bed was defined on kV-CT images using clips. CTVstandard was generated by adding a uniform three-dimensional 15 mm margin, and CTVtailored30 was generated by adding 30 mm minus the excision margin in three-dimensions. Concordance between CTVstandard and CTVtailored30 was quantified using conformity (CoI), geographical-miss (GMI) and normal-tissue (NTI) indices. An external-beam partial-breast irradiation (PBI) plan was generated to cover 95% of CTVstandard with the 95% isodose. Percentage-volume coverage of CTVtailored30 by the 95% isodose was measured.Median (range) coronal, superficial and deep excision margins were 15.0 (0.5–76.0) mm, 4.0 (0.0–60.0) mm and 4.0 (0.5–35.0) mm, respectively. Median CoI, GMI and NTI were 0.62, 0.16 and 0.20, respectively. Median coverage of CTVtailored30 by the PBI-plan was 97.7% (range 84.9–100.0%). CTVtailored30 was inadequately covered by the 95% isodose in 4/29 cases. In three cases, the excision margin in the direction of inadequate coverage was ⩽2 mm.CTVs based on 3D excision margin data are discordant with those defined using a standard uniform 15 mm TB–CTV margin. In women with narrow excision margins, the standard TB–CTV margin could result in a geographical miss. Therefore, wider TB–CTV margins should be considered where re-excision does not occur.

Neoadjuvant docetaxel treatment for locally advanced prostate cancer

The objective of the current study was to determine the histologic and molecular changes that occurred in patients with high-risk, localized prostate cancer (PCa) after neoadjuvant docetaxel chemotherapy. Patients who had locally advanced PCa (serum preoperative [initial] prostate-specific antigen [iPSA] level >or=15 ng/mL, or clinical >or=T2b disease, or biopsy Gleason score [GS] >or=8) and no evidence of metastatic disease received 6 doses of intravenous docetaxel (40 mg/m(2)) administered weekly for 6 weeks followed by radical prostatectomy (RP). The Wilcoxon signed-rank test was used to compare pretreatment and posttreatment markers. Twenty-eight patients completed chemotherapy and underwent RP at the Cleveland Clinic; none achieved a pathologic complete response. Pretreatment diagnostic prostate biopsies (PBx) were reviewed in all patients, and unstained sections of formalin-fixed tissue were available from 11 patients. The median patient age was 62 years (range, 49-72 years), and the median iPSA was 6.8 ng/mL (range, 2.5-24 ng/mL). At a median follow-up of 49.5 months (range, 23-72 months), 12 patients (43%) remained clinically and biochemically free of disease with no additional therapy, and 16 patients (57%) had biochemical failure. The pretreatment GS was 6 in 2 patients (7%), 7 in 10 patients (36%), 8 in 11 patients (39%) and 9 in 5 patients (18%). Two patients (7.1%) had organ-confined disease, and 23 patients (82.1%) had extraprostatic extension. Four patients (14.3%) had positive lymph nodes, and 11 patients (39.3%) had seminal vesicle involvement. Immunohistochemical (IHC) staining for a panel of markers involved in various cellular functions (alpha-methylacyl-coenzyme A racemase [AMACR], beta-tubulin I, beta-tubulin III, cyclin D1, p27, p21, Ki-67, p53, Bcl-2, and an apoptosis detection kit [ApopTag]) was performed on a tissue microarray that contained the posttreatment (RP) tissue specimens and on the PBx specimens, if available. When the IHC staining patterns were compared between PBx and RP specimens using the Wilcoxon signed-rank test, only p53 expression (P = .017) and Bcl-2 expression (P = .014) were found to be increased significantly after neoadjuvant docetaxel treatment. However, after performing the Bonferroni adjustment, these differences were no longer significant (P > .005). Ki-67, ApopTag, beta-tubulin I, and beta-tubulin III expression levels also were increased after treatment; however, the differences were not found to be statistically significant. The expression levels of AMACR, p27, p21, and cyclin D1 were comparable in pretreatment and posttreatment specimens. The current results indicated that, although it will require longer follow-up studies and larger numbers of patients to ascertain the value of neoadjuvant treatment, the negative findings of the current study may explain the lack of clinical response in patients who received neoadjuvant docetaxel for PCa. Although the results were subject to interpretation limits based on the study size, the increased expression of p53 and Bcl-2 that was detected after treatment using the Wilcoxon signed-rank test suggested that the apoptotic pathway may be an important target for this drug, and further investigation is warranted.

Neoadjuvant Docetaxel and Capecitabine and the Use of Thymidine Phosphorylase as a Predictive Biomarker in Breast Cancer

Thymidine phosphorylase (TP) induction by docetaxel is a proposed mechanism for the observed preclinical synergy of docetaxel and capecitabine (DC). We evaluated whether TP protein expression is increased by docetaxel and correlates with pathologic complete response (pCR) in breast cancer patients. Women with stage II to III breast cancer were given four cycles of neoadjuvant docetaxel 36 mg/m(2) i.v. over 30 min on days 1, 8, and 15 and capecitabine 2,000 mg/d, in two divided doses, on days 5 to 21 of a 28-day cycle. Radiology-directed biopsies of the breast tumors were done at baseline and 5 days after the first dose of docetaxel to evaluate TP expression. Following DC therapy, patients had core breast biopsies, and if residual disease was present, received four cycles of standard dose-dense doxorubin and cyclophosphamide (AC). The pCR rate was 26.9% (95% confidence interval, 11.6-47.8). Up-regulation of TP expression was not observed by either quantitative immunofluorescence (QIF) or immunohistochemistry. Radiology-directed core biopsy after neoadjuvant chemotherapy accurately predicted pathologic response in 88% (95% confidence interval, 69.8-97.6) of the cases. Neither level of TP expression nor TP up-regulation correlated with pCR. Significant toxicity resulted in therapy discontinuation in 3 of 26 patients. DC chemotherapy exhibited a similar pCR rate compared with standard taxane regimens, with increased toxicity. TP expression was not up-regulated after docetaxel and did not correlate with therapeutic response. Core breast biopsy after neoadjuvant chemotherapy accurately predicted pathologic response.

Locally advanced leiomyosarcoma of the urinary bladder: near-complete pathologic response to neoadjuvant gemcitabine and docetaxel

Leiomyosarcoma of the urinary bladder is a rare mesenchymal tumor with distinct pathologic features. Although radical cystectomy is the standard therapy for locally invasive disease, available literature appears to support the benefit of perioperative chemotherapy, similar to that seen with the more conventional urothelial malignancies. We report on a 77-year-old gentleman with locally advanced leiomyosarcoma of the bladder achieving a near-complete pathologic response to neoadjuvant chemotherapy with a unique regimen: gemcitabine and docetaxel. Further study of this anthracycline-sparing regimen is warranted.

Phase II neoadjuvant docetaxel/cisplatin followed by concurrent cisplatin/radiotherapy for locally advanced nasopharyngeal cancer

6059 Background: Neoadjuvant cisplatin/docetaxel are active agents for locally advanced nasopharyngeal cancer (LANPXCA). The efficacy and tolerability of neoadjuvant cisplatin/docetaxel followed by concurrent cisplatin with radiotherapy are explored in a phase II trial. Methods: From Jan 2003 to Jan 2005; 23 patients with LANPXCA stage III, IVA, IVB, (AJCC 2002), were treated with 3 cycles of neoadjuvant docetaxel 60mg/m2, 1 hour IV infusion D1 and cisplatin 60 mg/m2, 2 hours IV infusion D1 with prophylactic GSCF as 5μg/kg sc D3–7,(recycle D22). This was followed by 2 cycles of cisplatin 100 mg/m2, 2 hours IV infusion D1 , (recycle D22), concurrently with radiotherapy aiming at 70Gy / 35 fractions / 7 weeks. The median follow up was 27.9 months (18.3–47.3). Results: The median age was 38 years (16–68) and male to female ratio was 7.66:1. Neck mass 95.7%, neck pain 73.9%, nasal obstruction 65.2%, , headache 56.5%, impaired hearing 52.2%, and epistaxis 52.2% were the commonest symptoms. All patients had G3 squamous cell carcinoma. The majority of patients were stage IV 52.2% while 47.8 % were stage III. Grade one ECOG performance status was the commonest 52.2% while 47.8% were G2. The treatment was tolerable with commonest G3 acute toxicities were dysphagia 43.4% , and oral mucositis 8.7%. The commonest G3 late toxicities were dry mouth 17.4% and impaired hearing 13%. Complete remission was achieved in 22/23 patients 95.7% while 1/23 patients 4.3% was partial responder. Failure sites include; Distant; liver and/or bone 8.7%, local; skull base 4.3% or local and distant 4.3%.The Kaplan Meyer 47 month disease free survival was 82.61% while the 47 month overall survival was 91.3%. Conclusion: Neoadjuvant docetaxel / cisplatin followed by concurrent Cisplatin with radiotherapy is an effective and tolerable outpatient treatment for LANPXCA. No significant financial relationships to disclose.