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PubMed2000

Neoadjuvant hormone therapy: the Canadian trials.

The Canadian Urologic Oncology Group has carried out three studies of neoadjuvant hormonal therapy (NHT) in prostate cancer. The first, a study of 3 months of cyproterone acetate (CPA) 100 mg TID in patients undergoing external-beam radiation therapy, showed a benefit with respect to time to biochemical progression. There are no survival or clinical progression data available from this study. The second study involved 3 months of CPA prior to radical prostatectomy compared with radical prostatectomy alone and enrolled 200 patients. The probability of biochemical progression at 36 months was similar in the two groups (CPA 40%; surgery alone 30%; P = 0.3233). More recently, we have carried out a randomized trial of 3 v 8 months of leuprolide plus flutamide prior to radical prostatectomy in 547 patients. Patients were stratified by clinical stage, Gleason grade, and serum prostate specific antigen (PSA) concentration. In the 3- and 8-month groups, presurgery PSA concentrations were <0.1 ng/mL in 35% v 73%, and >0.3 ng/mL in 37% v 10%, respectively. In the 3- and 8-month groups, the positive margin rates were 17% and 5% and the organ-confined rates 71% and 91% (P < 0.01). One-year follow-up is now available on the entire cohort. Data regarding time to biochemical and clinical progression and overall and disease-specific survival will be required to determine whether this change in the pathologic findings translates into a patient benefit.

Androgen Antagonists↗

PubMedDate not supplied

Breast-conserving therapy after neoadjuvant chemotherapy: long-term results.

The purpose of this study was to determine patterns of ipsilateral breast tumor recurrence (IBTR) and local-regional recurrence (LRR) after neoadjuvant chemotherapy and breast-conserving therapy (BCT). A total of 153 breast cancer patients were treated with neoadjuvant chemotherapy followed by conservative surgery and radiation therapy between 1980 and 2002. The clinical stage (American Joint Committee on Cancer [AJCC] 1997) at diagnosis was IIA in 22%, IIB in 28%, IIIA in 39%, and IIIB in 11%. The prechemotherapy T size distribution was less than 2 cm in 5 patients, 2.1-5 cm in 100 patients, and greater than 5.1 cm in 48 patients. Sixty-seven patients (44%) underwent cyclophosphamide, methotrexate, and 5-fluorouracil (CMF)-based chemotherapy and 86 (56%) underwent Adriamycin-based chemotherapy. Thirty-seven patients (24%) had a complete pathologic response in the breast. All procedures were performed by a single surgeon (G.F.S.). The surgery was local excision alone in 19 patients, local excision and axillary lymph node dissection (ALND) in 130 patients, and ALND alone in 4 patients. Eleven patients had positive surgical margins. Rates of LRR-, IBTR-, and distant metastasis (DM)-free survival were calculated by the Kaplan-Meier method. Patient and pathologic variables were then analyzed in an attempt to identify predictors of clinical outcome. With a median follow-up period of 55 months (range 6-200 months), eight patients developed LRR, five of which were classified as IBTR. Five- and 10-year actuarial rates of LRR-free, IBTR-free, and DM-free survival were 93% and 88%, 96% and 91%, and 70% and 58%, respectively. Pretreatment and pathologic parameters that positively correlated with IBTR were advanced stage (p = 0.03) and margin positivity (p = 0.04). No other clinical factors were predictive of higher recurrence. BCT results in a low rate of IBTR and LRR in appropriately selected patients. Advanced stage at presentation is associated with increased risk of IBTR, although overall recurrence is low. In selected cases, BCT is safe and an effective alternative to mastectomy.

Adult↗

PubMed2002

Transanal excision of locally advanced rectal cancers downstaged using neoadjuvant chemoradiotherapy.

BACKGROUND: Our institution has previously demonstrated a survival advantage conferred by preoperative neoadjuvant therapy for locally advanced rectal cancers. We now report our results using transanal excision as definitive surgical therapy in a selected group of patients who experienced significant downstaging of T3 rectal cancers after neoadjuvant therapy. STUDY DESIGN: Seventy-four patients diagnosed with locally advanced (T3) rectal cancers were treated with neoadjuvant chemoradiotherapy. After neoadjuvant therapy, 11 (14.9%) patients who had significant downstaging of their tumors were selected to undergo transanal excision of their residual rectal cancers. Intraoperative cryostat evaluation was used to confirm negative margin status, and all patients were subsequently followed with routine endoscopy, transrectal ultrasonography, and digital rectal examinations. RESULTS: Tumors were located between 1 cm and 7 cm from the anal verge (mean 4.3 +/- 0.6 cm), and were located in lateral, anterior, and posterior positions. Mean followup was 55.2 +/- 8.9 months (median 47.9 months). Imaging studies using CT, MRI, transrectal ultrasonography, or combination demonstrated suspicious lymph nodes in three patients. After neoadjuvant therapy, these lymph nodes were no longer demonstrated in two patients. There were no local recurrences, nodal metastases, or operative mortalities. One patient (9%) developed distant metastases (pulmonary nodules), and remains alive 30 months after transanal excision. One patient (9%) experienced sphincter laxity, which was successfully repaired, and is now asymptomatic. One patient (9%) developed postoperative urgency that resolved spontaneously. CONCLUSIONS: In patients who have initial bulky (T3) lesions, and experience significant downstaging after neoadjuvant chemoradiotherapy, transanal excision appears to be a safe and effective treatment, preserving sphincter function and avoiding laparotomy.

Adult↗

PubMed2004

Feasibility of radical prostatectomy after neoadjuvant chemohormonal therapy for patients with high risk or locally advanced prostate cancer: results of a phase I/II study.

PURPOSE: We determined the feasibility of radical prostatectomy after neoadjuvant chemohormonal therapy in locally advanced (stage T3 or greater) and/or high risk tumors (Gleason 8 to 10 and/or serum prostate specific antigen (PSA) greater than 20 ng/ml). MATERIALS AND METHODS: Enrollment criteria included clinical stage T1 to 2 with any Gleason grade and PSA greater than 20 ng/ml, clinical stage T3 to 4 with any serum PSA or Gleason grade, or any clinical stage with biopsy Gleason grade of 8 to 10 and any serum PSA. All patients received neoadjuvant hormonal therapy during chemotherapy (4 cycles of paclitaxel and carboplatin and estramustine) followed by radical prostatectomy. Nerve sparing was decided on an individual basis and a nerve graft was offered to those who underwent unilateral or bilateral nerve resection. Perioperative morbidity, mortality and delayed complications were assessed. RESULTS: A total of 36 patients were enrolled. After chemohormonal therapy clinical stage was less in 39% of patients and greater in 36%. Bilateral nerve sparing was performed in 3 patients and the remaining 33 underwent either unilateral or bilateral neurovascular bundle resection with nerve grafts performed in 17 (52%). Deep vein thrombosis (22%) was the most frequent complication of chemotherapy. Minor postoperative complications occurred in 6 patients. At a median followup of 29 months (range 5 to 51) after radical prostatectomy 32 (89%) were continent and 5 (15%) preoperatively potent men remained potent. The positive surgical margin rate was 22%. Of all subjects 45% remain free from biochemical recurrence. CONCLUSIONS: Neoadjuvant chemohormonal therapy followed by radical prostatectomy can be performed with low morbidity. Positive surgical margin rates are low. This approach yielded good local control of disease, however impact on tumor recurrence and survival is not known.

Adult↗

PubMed2001

[Local staging with magnetic resonance imaging after neoadjuvant hormonal therapy for prostate cancer].

We retrospectively studied the staging accuracy of magnetic resonance (MR) imaging after neoadjuvant hormonal therapy (NAH) for 21 localized prostate cancers. MR imaging was performed using a 1.5-Tesla magnetic resonance system with a pelvic phased array coil. T2-weighted MR images were obtained on axial and coronal planes, and T1-weighted MR images using the dynamic technique with Gd-DTPA bolus enhancement were obtained in axial planes for each patient. On T2-weighted imaging, the signal intensity of the normal tissue in the peripheral zone became lower after NAH. Therefore, it was more difficult to detect residual malignant lesions in many cases than before NAH. The accuracy of T staging for prostate cancer after NAH in MRI was 71%. The accuracy, sensitivity, and specificity of the extracapsular invasion was 76%, 0% and 94%, respectively, and those of the seminal vesicular invasion 85%, 0% and 100%, respectively. While 2 of the 4 patients judged as downstaged cases in MRI showed corresponding pathological findings, 5 of the 21 cases (23.8%) were underdiagnosed. Local staging with only MRI for prostate cancer after NAH seems to have limits in applicability.

Aged↗

PubMed2002

Neoadjuvant hormonal therapy prior to radical prostatectomy: evaluation of pathological downstaging and biochemical relapse.

OBJECTIVES: The effect of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy (RP) on pathological downstaging of prostate cancer and biochemical relapse of serum prostate specific antigen (PSA) level was evaluated. MATERIALS AND METHODS: Twenty selected patients with prostate cancer, who were treated with hormonal therapy and demonstrated biochemical downstaging by reduction of PSA prior to RP and bilateral pelvic node dissection at the Tohsei National Hospital between January 1997 and August 2001, are reported on. The complete RP specimens of these 20 men were used for accurate evaluation of the pathological stage. All 20 patients received NHT; ten patients were treated with leuprolide plus flutamide and 10 received leuprolide plus chlormadinone acetate (CMA). RESULTS: Decreases in serum PSA values were demonstrated from a pre-hormonal average of 49.7 ng/ml to an average of 0.52 ng/ml after NHT. Of the three clinical stages, A2-C, for cancer patients, two of the 20 patients had stage A2, two had stage B1, nine had stage B2, and seven had stage C. Of the 20 patients with biochemical downstaging, two had pathological stage B1, seven had pathological stage B2, eight had pathological stage C, and three had positive pelvic lymph nodes. Ten (50%) of the 20 patients were reported to have positive surgical margins. Seminal vesical extension was observed in two cases, and penetration was not observed. Positive nodes were identified in three (15%) patients. Among the seven clinical stage C patients, one had pathological stage B1 disease and two had pathological stage B2. Four of nine patients with clinical stage B2 prostatic cancer had pathological stage C disease. The actuarial incidence of a rising PSA at 3 years for the leuprolide plus CMA group was 28.9% compared with 37.5%for the group receiving leuprolide plus flutamide. The cases of biochemical relapse did not necessarily indicate a high stage and had no tendency to be high for baseline PSA level, positive margin rates or Gleason scores. CONCLUSIONS: A significant decrease in the rate of penetration could be observed after NHT, though it was not so effective for pathological downstaging, and changes in the preoperative PSA level did not predict those patients who might have a favorable result.

Adenocarcinoma↗

PubMed1999

Pathologic Handling and Reporting of Prostate Tissue Specimens in Patients Receiving Neoadjuvant Hormonal Therapy: Report of the Pathology Committee.

Prior meetings of the International Conference on Neoadjuvant Hormonal Therapy in Prostate Cancer identified areas of concern in the pathologic analysis of post-treatment specimens. In response, a pathology subcommittee was formed to address the questions that had been raised. Recommendations are made here concerning pretreatment biopsy review and reporting, handling and reporting of radical prostatectomy specimens, Gleason scoring of treated cancer, grading of therapy effect, role of immunohistochemistry procedures, and the significance of high-grade prostatic intraepithelial neoplasia. Neoadjuvant trials with both surgery and radiation therapy were considered in drawing up these recommendations.

Journal Article↗

PubMed1997

Prediction of response to neoadjuvant chemoendocrine therapy in primary breast carcinomas.

Our aim was to determine whether biological molecular markers can predict response to neoadjuvant chemoendocrine therapy in patients with early breast cancer. Ninety patients (median age 56 years; range, 28-69 years) with primary operable breast carcinoma were studied. They were treated with four 3-weekly cycles of chemotherapy with mitozantrone, methotrexate (+/- mitomycin C), and tamoxifen prior to surgery. Fine-needle aspiration was used to obtain samples from patients prior to therapy, and the following parameters were assessed: estrogen receptor (ER), progesterone receptor (PgR), p53, Ki67, Bcl-2, and c-erbB-2 measured by immunocytochemistry, and ploidy and S-phase fraction (SPF) by flow cytometry. The tumors of 78% of the subjects responded (complete response, 9%; partial response, 69%) and 22% did not (no change, 20%; progressive disease, 2%). Response rates according to disease stage and patient age were as follows: T1, 74%; T2, 79%; T3/T4, 78%; age </=50 years, 76%; >50, 79% (P = not significant). Response rates for other parameters were as follows: ER-positive, 82%, and -negative, 70%; PgR-positive, 86%, and -negative, 71%; p53-positive, 74%, and -negative, 81%; Bcl-2-positive, 85%, and -negative 61%; c-erbB-2-positive, 57%, and -negative, 93%; Ki67 high, 77%, and low, 81%; SPF high, 77%, and low, 77%; aneuploid, 71%; and diploid, 85%. Only the difference for c-erbB-2 was statistically significant (P = 0.007). A trend for higher response rates to neoadjuvant chemoendocrine therapy for tumors that were positive for ER, PgR, and Bcl-2 was observed but did not reach statistical significance. Tumors negative for c-erbB-2 had a higher response rate, which was statistically significant. In contrast, Ki67, ploidy, SPF, and p53 failed to predict for response.

Adult↗

PubMed1996

Effect of neoadjuvant endocrine therapy (combined androgen blockade) on normal prostate and prostatic carcinoma. A randomized study.

The morphologic changes induced by neoadjuvant combination endocrine therapy were evaluated in prostatectomy specimens from patients diagnosed with localized prostate cancer. These patients participated in a prospective, randomized clinical trial investigating the effect of 3 months of combination therapy with flutamide and an LHRH agonist prior to radical prostatectomy versus radical prostatectomy alone. Ninety-six radical prostatectomy specimens processed according to the same protocol were evaluated without knowledge of prior treatment. Forty-seven patients were randomly assigned to the neoadjuvant combination therapy group and 49 to the control arm. Compared with the control group, several changes were strongly and significantly associated with exposure to neoadjuvant combination therapy. The nonmalignant prostatic tissue showed strong prominence and hyperplasia of the basal cell layer, accompanied by epithelial cell vacuolization and markedly reduced occurrence of prostatic intraepithelial neoplasia (p < 0.001) after combination therapy. Prostate cancer tissue, on the other hand, showed smaller nucleoli (p < 0.001), cell vacuolization (p < 0.001), rare intraluminal crystalloids (p < 0.001), higher Gleason grade (p < 0.001), lower prevalence of capsular penetration (p < 0.001), and less frequent invasion of the perineural spaces (p < 0.001) and surgical margins (p = 0.002). Tumor volume, was also reduced by more than 40% in the treated group (p = 0.007). The present findings show that preoperative endocrine combination therapy induces highly characteristic changes in both nonmalignant and cancerous prostatic tissue. Furthermore, following endocrine treatment, the surgical margins are less likely to be involved by cancer and capsular penetration is reduced.

Adult↗

PubMed2005

[Short-term neoadjuvant hormone therapy enhanced expression of clusterin in prostate cancer].

OBJECTIVE: To define changes in clusterin expression following short-term neoadjuvant hormone therapy (NHT) and its biological significance in prostate cancer tissues. METHODS: Twenty-six archival radical prostatectomy (RP) specimens without receiving NHT, 19 needle biopsies and corresponding 19 RP specimens following 3-month NHT, were subjected to immunohistochemical clusterin staining. RESULTS: Staining for clusterin was mainly found in cytoplasm and part of extracellular matrix. Clusterin expression was significantly greater in RP specimens with preoperative NHT (t = 2.91, P < 0.01); Needle biopsies obtained before NHT consistently demonstrated lower staining intensity (1.42 +/- 0.51) than corresponding RP specimens (2.16 +/- 0.60) following 3-month NHT (t = 7.10, P < 0.01). CONCLUSIONS: Upregulation of clusterin in part accounts for malignant progression of prostate cancer through its anti-apoptotic action following androgen withdrawal. These findings support that adjuvant therapy targeting clusterin may enhance androgen ablation therapy in advanced prostate cancer.

Aged↗

PubMed2006

[8-month neoadjuvant hormonal therapy before radical prostatectomy for high-risk prostate cancer].

PURPOSE: To evaluate the clinicopathological outcomes of 8 months of neoadjuvant hormonal therapy (NHT) prior to radical prostatectomy for high-risk prostate cancer. PATIENTS AND METHODS: A multi-institutional prospective trial was performed between July 2000 and May 2003 involving high-risk prostate cancer patients without metastasis, including 21 who received 8 months of NHT before radical prostatectomy. High-risk group was defined as clinical stage > or =T2c and/or prostate-specific antigen (PSA) >20 ng/ml and/or Gleason score > or =8. PSA values were considered elevated (biochemical failure) if values of 0.1 ng/ml or greater were obtained. RESULTS: Median of initial PSA levels before prostate biopsy was 27.6 ng/ml (8.5-80.7 ng/ml), and median of pre-operative PSA levels after NHT was 0.28 ng/ml (0.02-4.2 ng/ml). There were 5 patients (23.8%) with lower limit of PSA detection (less than 0.02 ng/ml) in 8 months after NHT. The clinical T stage was T1c in 9 patients (42.9%), T2a-b in 8 patients (38.1%), T2c in 3 patients (14.3%), and T3a in 1 patient (4.8%). The median follow-up was 25 months (range 4 to 37). There were 2 patients (9.5%) in pT0, 5 patients (23.8%) with positive surgical margin, 5 patients (23.8%) with extracapsular extension (ECE) and 3 patients (14.3%) with seminal vesicle involvement (SVI). Biochemical failure was occurred in 9 of 21 (42.9%) including of one pT0. Range of time to postoperative biochemical failure was 2 to 25 months (median 6 months) and most of biochemical failure was found within 12 months after surgery. Biochemical failure rate was significantly higher in patient with positive SVI (p = 0.0308) and higher in patients with pre-operative PSA levels of more than 0.1 ng/ml (p = 0.0836), positive ECE (p = 0.0545) and positive surgical margin (p = 0.0545). CONCLUSION: Biochemical failure was frequent after this combined treatment, even in a pT0 case. Long-term follow-up of patients is needed to assess the impact of this therapy on mortality.

Aged↗

PubMed2006

The quality of life of men with locally advanced prostate cancer during neoadjuvant hormone therapy: data from the Medical Research Council RT01 trial (ISRCTN 47772397).

OBJECTIVE: To explore patients' quality of life (QoL) during neoadjuvant hormone therapy (HT) using data from the Medical Research Council RT01 trial of standard- (64 Gy/32-fraction) and high- (74 Gy/37-fraction) dose radiotherapy (RT, both given conformally). PATIENTS AND METHODS: Of the 843 patients randomized to the RT01 trial, 316 completed the Functional Assessment Of Cancer Therapy core questionnaire with its additional prostate subscale, and the Short Form-36 Health Survey questionnaire with the University of California-Los Angeles Prostate Cancer Index before HT and again before starting RT. Three predefined QoL hypotheses were generated to focus the analyses. RESULTS: For the three primary QoL analyses there was evidence that sexual functioning deteriorated, urinary function did not change, and there was a slight decline in physical well-being after > or = 3 months of HT. Sensitivity analyses confirmed these findings. Exploratory analyses also suggested that role functioning deteriorated, sleep was more disturbed, and there was an increase in fatigue. However, overall QoL was not reported to be affected and patients indicated an improvement in attitude and satisfaction with treatment. CONCLUSIONS: In this group of men, many of whom reported reduced sexual functioning before treatment, the additional decline during HT seemed to be generally accepted as the price to pay for an appropriate cancer treatment. Nevertheless, these changes need to be discussed with patients before HT is commenced.

Aged↗

PubMed2003

Neoadjuvant photodynamic therapy as a new approach to treating hilar cholangiocarcinoma: a phase II pilot study.

BACKGROUND: Only 20-30% of patients with hilar cholangiocarcinomas (CC) are candidates for potentially curative resection. However, even after curative (R0) resection, these patients have a disease recurrence rate of up to 76%. The current prospective Phase II study investigated photodynamic therapy (PDT) as a neoadjuvant treatment for CC. METHODS: Seven patients with advanced proximal bile duct carcinoma were evaluated. Patients were treated with PDT at the area of tumor infiltration and 2 cm beyond and underwent surgery after a median period of 6 weeks (range, 3-44 weeks). RESULTS: One patient had a Bismuth-Corlette Type II tumor, two patients had Type IIIa, one patient had Type IIIb, and three patients had Type IV. Cholestasis parameters after PDT decreased significantly. No relevant adverse events from PDT occurred except for minor intraoperative phototoxicity in one patient. Three patients underwent right-sided liver resections, two patients underwent left-sided liver resections, and one patient received a combined hilar resection with partial pancreatoduodenectomy (PD) due to tumor extension into the distal bile duct. Liver transplantation and PD were performed in another patient. In all patients, R0 resection was achieved. Four patients developed minor surgical complications, even though the bilioenteric anastomoses were sewn to PDT-pretreated bile ducts. No viable tumor cells were found in the inner 4 mm layer of the surgical specimens. The PDT-pretreated epithelium of the tumor-free proximal resection margins exhibited only minimal inflammatory infiltration. Tumors recurred in 2 patients 6 and 19 months after surgery. The 1-year recurrence free survival rate was 83%. CONCLUSIONS: Neoadjuvant PDT for hilar CC is a low-risk procedure with efficient selective destruction of the superficial 4 mm layer of bile duct tumor without complications exceeding series without neoadjuvant PDT. Neoadjuvant PDT should be evaluated prospectively to determine whether it reduces the rate of local disease recurrence after potentially curative resection.

Adult↗

PubMed2004

Multimodal treatment strategies combining neoadjuvant hormonal therapy and/or chemotherapy with radical prostatectomy in high-risk localised prostate cancer.

By combining the readily available clinical parameters of tumour stage, Gleason score of the diagnostic biopsy specimen and serum prostate-specific antigen level, men with newly diagnosed prostate cancer can be assessed as to their risk of treatment failure after radiotherapy or radical prostatectomy. For men considered to be at high-risk of treatment failure after local therapy alone, multimodal treatment strategies may result in improved cancer-control outcomes. This strategy has proven effective in the setting of clinical stage T3 - T4 tumours in which the combination of radiotherapy followed by hormonal therapy has improved patient survival. The benefit of neoadjuvant or adjuvant hormonal and/or chemotherapy followed by radical prostatectomy in this setting is unclear but is the subject of ongoing or planned Phase III clinical trials. These studies will help examine the role of multimodal treatment strategies in these high-risk patients.

Antineoplastic Agents, Hormonal↗

PubMed2000

Oxaliplatin. A review of its pharmacological properties and clinical efficacy in metastatic colorectal cancer and its potential in other malignancies.

UNLABELLED: Oxaliplatin is a platinum compound that inhibits DNA synthesis, primarily by causing intrastrand cross-links in DNA. Oxaliplatin has a broad spectrum of antineoplastic activity and has demonstrated a lack of cross-resistance with other platinum compounds. In patients with metastatic colorectal cancer, intravenous oxaliplatin has been trialled as a monotherapy and in combination with other agents. The highest response rates were achieved when oxaliplatin was used in combination with fluorouracil/folinic acid (leucovorin; calcium folinate), typically > or = 50% in the first-line setting and 13 to 45% as a second-line therapy. First-line triple therapy with oxaliplatin and fuorouracil/folinic acid achieved significantly higher response rates and longer median progression-free survival than fluorouracil/folinic acid therapy alone. However, no significant difference in the median duration of overall survival was found. This may be a consequence of the subsequent use of oxaliplatin and/or surgery after disease progression in patients who relapsed after fluorouracil/folinic acid therapy alone. Neoadjuvant therapy with oxaliplatin/fluorouracil/folinic acid has proven beneficial in enabling surgical removal of previously unresectable liver metastases. In 2 studies, surgery with curative intent was performed in 16 and 51% of patients with initially unresectable liver metastases following oxaliplatin/fluorouracil/folinic acid therapy; the 5-year survival rates were 40 and 50%, respectively. In patients with advanced ovarian cancer, first-line therapy with oxaliplatin/cyclophosphamide achieved an objective response rate which did not differ significantly from that of cisplatin/cyclophosphamide (33 vs 42%). In addition, oxaliplatin has shown efficacy in patients with platinum-pretreated ovarian cancer and achieved objective response rates similar to paclitaxel in this setting (16 vs 17%). Promising results have also been found with oxaliplatin in patients with non-Hodgkin's lymphoma, breast cancer, mesothelioma and non-small cell lung cancer. Reversible, cumulative, peripheral sensory neuropathy is the principle dose-limiting factor of oxaliplatin therapy. Haematological and gastrointestinal toxicities occur frequently but are generally mild to moderate in intensity. CONCLUSION: Oxaliplatin in combination with fluorouracil/folinic acid is an effective treatment option for patients with metastatic colorectal cancer, both as a first-line therapy and in patients refractory to previous chemotherapy. Although preliminary results failed to show any overall survival advantage of this regimen over fluorouracil/folinic acid alone, this may be a consequence of trial design and requires further examination. Additional clinical investigation of oxaliplatin in patients with other cancers is warranted given the promising results achieved in early trials, most notably in patients with platinum-pretreated ovarian cancer.

Animals↗

PubMedDate not supplied

Immunohistochemical study of cyclooxygenases in prostatic adenocarcinoma; relationship to apoptosis and Bcl-2 protein expression.

BACKGROUND: Cyclooxygenase (COX) is a key enzyme in the conversion of arachidonic acid to prostaglandins and other eicosanoids. A recent report has indicated a selective COX-2 inhibitor resulted in increased apoptosis and down-regulated bcl-2 expression in the androgen-sensitive human prostate cancer cell. We investigated the localization of COXs in prostatic adenocarcinoma and the possible correlation of androgen blockade with its expression. MATERIALS AND METHODS: The immunohistochemical expression of COX-1, COX-2 and bcl-2 protein was studied using paraffin-embedded archival tissues both before and after hormonal therapy. The number of apoptotic cells was also determined. RESULTS: Immunohistochemistry for COX-1, not COX-2, showed the constitutive expression in the stroma of normal prostate. The expression of COX-2 protein was detected less often than that of COX-1 protein in most cases of prostatic adenocarcinoma before hormonal therapy. Neoadjuvant hormonal therapy induced the expression of COX-2 protein in smooth muscle cells, fibroblasts and adenocarcinoma cells. The expression after hormonal therapy was possibly correlated with the bcl-2 protein expression. CONCLUSION: The present study is the first to demonstrate the immunohistochemical expression of COXs in human prostate tissue and indicated that COXs were relevant to homeostasis and tumor development of the prostate.

Adenocarcinoma↗

PubMed2006

Retrospective analysis on prognostic impact of adjuvant chemotherapy in the patients with advanced and resectable oral squamous cell carcinoma.

PURPOSE: The effect of adjuvant chemotherapy on oral squamous cell carcinoma (SCC) is unclear mainly because there have been a few studies which evaluate the efficacy of adjuvant chemotherapy. The purpose of this retrospective study was to analyze the efficacy of adjuvant chemotherapy in the patients with advanced and resectable oral SCC. METHODS: 41 patients in whom advanced SCC (stage III and IV) was completely removed were included in this study. The impact of multiple variables including T-classification, degree of differentiation, mode of invasion, number and level of cervical metastatic node, pre-and post-operative radiation therapy, neoadjuvant chemotherapy, and adjuvant chemotherapy on survival and control of local relapse or distant metastasis was assessed using the stepwise Cox proportional hazards model. RESULTS: The level of neck node metastasis (p<0.02) was a significant independent predictor for cause-specific survival and adjuvant chemotherapy was of borderline significance (p=0.07). The number of neck node metastasis (p<0.01) and adjuvant chemotherapy (p<0.01) were significantly related with disease free survival. CONCLUSION: The results of this retrospective study suggested that adjuvant chemotherapy had a significant benefit in improving disease free survival.

Administration, Oral↗

PubMed1998

[Clinical stage T3 prostate cancer: natural history, therapeutic choices and their results].

Clinical stage T3 prostate cancer is ambiguous both in terms of its definition and its place in the natural history of the disease, and there is no consensus concerning its treatment. In a review of the literature, 148 articles were selected and analysed from the Medline database over a 14-year period (1983-1997). Single-agent therapy: Radiotherapy and radical prostatectomy: it is unlikely that these treatments can cure clinical stage T3 prostatic cancer, except perhaps for a small minority of patients actually presenting with overstaged pT2 disease or certain forms of low-grade pT3. Neither treatment appears to have any advantage over the other-Endocrine therapy: it has been proposed as exclusive treatment at this stage. Few studies have been reported. However, many authors consider this choice to be legitimate, because one-half of patients already have lymph node involvement. Combination therapy: Radiotherapy and endocrine therapy: recent studies comparing exclusive external beram radiotherapy with endocrine therapy show an advantage in favour of combination therapy. Total prostatectomy and endocrine therapy: neoadjuvant endocrine therapy does not provide any advantage. Adjuvant endocrine therapy improves local control and progression-free survival. Adjuvant radiotherapy and radical prostatectomy provides no advantage for T3. The choice of treatment for stage T3, N0, M0 obviously depends on the patient's general state and life expectancy. If the option of a curative treatment in a young subject can be reasonably considered, combination therapy should be preferred.

Adult↗