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At least 217 records · Page 12Linked to original sources
PubMed2006

Oestrogen receptor beta and neoadjuvant therapy with tamoxifen: prediction of response and effects of treatment.

In order to elucidate the relative importance of oestrogen receptor (ER)alpha, ERbeta and an ERbeta variant (ERbeta2/betacx) in the response of breast cancers to tamoxifen, tumour levels of each receptor were assessed in 36 patients before and after 3 months of neoadjuvant treatment with tamoxifen (20 mg daily). All patients were postmenopausal women presenting with large ERalpha-positive breast cancers. Clinical response to treatment was assessed by tumour volume changes as determined from sequential ultrasounds and pathological response by comparison of the tumour morphology before and after treatment. Of 33 cases, 23 (70%) were classified as having a clinical response and 16 (48%) as having a response pathologically. All tumours stained positively for ERalpha and ERbeta and 15 out of 33 (45%) for ERbeta2/betacx. There were no significant differences in quantitative expression of any receptor between tumours that subsequently responded and that did not, whether response was assessed clinically or pathologically. Tamoxifen treatment was associated with a decrease in ERalpha, but an increase was the most frequent change (17 out of 33) in ERbeta, and no consistent change was evident in staining of the ERbeta2/betacx variant. In summary, ERbeta1 and ERbeta2/betacx variant protein are detected in ERalpha-positive breast tumours but their expression is not associated with a response to tamoxifen. Differential changes in ERalpha and ERbeta were seen with treatment.

Aged↗
PubMedDate not supplied

Postchemotherapy MRI overestimates residual disease compared with histopathology in responders to neoadjuvant therapy for locally advanced breast cancer.

UNLABELLED: The utility of breast magnetic resonance imaging in patients receiving neoadjuvant chemotherapy is not well defined. We compared serial magnetic resonance imaging examinations with histologic posttreatment examinations in patients treated with primary chemotherapy for locally advanced breast cancer. PATIENTS AND METHODS: Eligible patients with locally advanced breast cancer received doxorubicin 60 mg/m(2) and docetaxel 60 mg/m(2) (with granulocyte colony stimulating factor support) every 14 days for a maximum of six cycles. Breast magnetic resonance imaging was performed at baseline and repeated every two cycles. Surgery (either local excision or mastectomy) was performed after six cycles in responding or stable patients. Residual tumor size on pathology and preoperative magnetic resonance imaging was compared; concordance was defined as a < or = 0.5-cm difference. RESULTS: To date, three of 17 enrolled subjects (17.6%) attained pathologic complete response, and three additional patients attained near pathologic complete response, with residual foci of < or = 1 mm. Of these six patients, only one was disease-free by magnetic resonance imaging. Discordance between magnetic resonance imaging findings and pathologic evaluation was found in four of six patients (66.6%) who obtained pathologic complete response or near pathologic complete response. In the three patients in whom four axillary lesions were followed with magnetic resonance imaging, discordance was found in all four lesions, with magnetic resonance imaging overestimating pathologic disease in all cases. DISCUSSION: Our findings caution that magnetic resonance imaging may frequently overestimate residual invasive carcinoma after neoadjuvant chemotherapy. These results contradict previous studies suggesting that postchemotherapy magnetic resonance imaging may underestimate residual cancer. The use of magnetic resonance imaging in evaluating response to therapy in locally advanced breast cancer should be further studied.

Adult↗
PubMed2002

Assessing the predictive value of clinical complete response to neoadjuvant therapy for rectal cancer: an analysis of 488 patients.

BACKGROUND: Patients with transmural or node-positive rectal cancer benefit from the addition of chemoradiation to surgical resection. Administration of the chemoradiation (combined modality therapy) preoperatively has gained popularity in recent years. Some patients undergo apparent complete tumor regression after preoperative combined modality therapy, and controversy exists about the proper management of these patients. Some investigators have proposed that such patients should simply be observed and not undergo resection. STUDY DESIGN: The purpose of this study was to determine the significance of clinical complete response to preoperative combined modality therapy. Specifically, we have attempted to determine the frequency with which a clinical complete response (based on the absence of detectable tumor on preoperative digital rectal examination and proctoscopy) correlates with a pathologic complete response (based on the absence of cancer cells in the resected specimen). A retrospective review of the clinical and pathologic characteristics of 488 patients from the Memorial Sloan-Kettering prospective colorectal database who received preoperative chemoradiation followed by resection for primary rectal cancer was performed. The indications for preoperative therapy included clinical or ultrasound T3 or T4 tumors or node-positive disease. RESULTS: The clinical complete response rate to preoperative therapy was 19%. All patients underwent resection subsequent to preoperative therapy regardless of response. The pathologic complete response rate among all patients was 10%. The pathologic complete response rate among clinical complete responders was 25%. Clinical complete response was a significant predictive factor for pathologic complete response, but the majority (75%) of clinical complete responders had persistent foci of tumor that were not detectable on preoperative examination or proctoscopy. CONCLUSIONS: Clinical complete response to preoperative therapy as determined by preoperative digital rectal examination and proctoscopy or EUA is not an accurate predictor of pathologic complete response. A significant percentage of clinical complete responders have persistent deep tumors or nodal involvement. We do not recommend making treatment decisions based solely on the absence of clinically palpable or visible tumor after chemoradiation. Our data suggest that all acceptable-risk patients with a diagnosis of primary rectal cancer should undergo resection, regardless of their response to preoperative therapy.

Adult↗
PubMed2006

[Predictive factors in esophageal cancer after neoadjuvant therapy].

BACKGROUND: Preoperative chemoradiation therapy (PCX) was introduced to improve the outcome of patients with oesophageal cancer (EC), but conflicting results have been released. Some 20-30% of patients show a complete pathological response, however, the perioperative morbidity and mortality is increased. To search for factors indicating response prior to the onset of PCX we investigated the proliferative activity (MIB-1), the expression of vascular endothelial growth factor (VEGF), and the capillary density (CD34) tissue specimens of ECs were available by endoscopy prior to the start of the treatment. METHODS: Forty-six (MIB-1) and 21 (VEGF, CD34) tissue specimens of ECs were available from 56 patients undergoing pretherapeutic endoscopy, PCX and surgery. Perioperative morbidity was divided into surgery and non-surgery related morbidity. MIB-1, VEGF and CD34 expression were investigated immunohistochemically. Multivariate analysis was carried out to prove independence of investigated variables. RESULTS: Postoperative morbidity was noticed in 54 of 56 operated patents. Eight of 56 patients who received PCX died in hospital. Survival was significantly different between the group of complete responders (n=14) and non-responders (n=23; P = 0.0026). None of investigated tumour samples from patients with a complete response (CR) had a proliferation index of less than 45. Tumour samples from patients with a CR showed a VEGF expression of 10.7 compared with 36.58 of tumours with no response (P = 0.035). CD34 expression showed a correlation with VEGF expression. The relation of mean indices of VEGF expression and proliferative activity in tumours from patients with complete, partial or no response was 10. 7:58.8, 18.3:53.8 and 36.6:43.5, respectively. CONCLUSIONS: According to these results, it may be expected that tumours with a VEGF/MIB-1 ratio of 1:5 or less prior to PCX will respond to this therapy.

Adult↗
PubMed2004

A Phase II study of docetaxel and carboplatin as neoadjuvant therapy for nasopharyngeal carcinoma with early T status and advanced N status.

BACKGROUND: Promising results from a Phase II trial of induction chemotherapy and sequential radiotherapy for advanced nasopharyngeal carcinoma (NPC) at The University of Texas M. D. Anderson Cancer Center (Houston, TX) and two retrospective reviews of the authors' historical experience with NPC demonstrated that distant failure was directly correlated with advanced lymph node status. Furthermore, local control was excellent for patients with T1-3 disease that was managed with radiation alone or with a sequential approach involving chemotherapy. Neoadjuvant chemotherapy (primarily with cisplatin + 5-fluorouracil) was associated with a significantly decreased risk of distant metastasis and with improved survival. Based on these findings, the authors evaluated a novel induction regimen involving docetaxel and carboplatin for patients with previously untreated T1-2N2-3M0 NPC. METHODS: Docetaxel (80 mg/m2 on Day 1) and carboplatin (to an area under the time-concentration curve of 6 on Day 1) were administered every 21 days for 3 cycles, after which radiotherapy was administered. NPC was restaged with magnetic resonance imaging and nasopharyngoscopy 3 weeks after the completion of chemotherapy and 6 weeks after the completion of radiotherapy. RESULTS: Over 5 years, 18 patients were enrolled in the study. Grade 4 neutropenia and Grade 2 fatigue were observed in 51% and 28% of chemotherapy courses, respectively. After chemotherapy, 2 patients had complete responses, 14 had partial responses, 1 had a minor response, and 1 had progressive disease. The latter two patients and one patient who had a partial response underwent off-study chemoradiotherapy. After radiotherapy or chemoradiotherapy, 12 patients had complete responses and 6 had partial responses. Seven patients had recurrent disease; two had local recurrences, and five had distant metastases. CONCLUSIONS: Although unlikely to be superior to cisplatin + 5-fluorouracil, the trial regimen could be administered quickly in the outpatient setting, was logistically more convenient for the patient, and was devoid of serious nonhematologic toxic effects. We believe that the risk-based approach examined in the current study merits further investigation.

Adult↗
PubMed2006

Pancreaticoduodenectomy after neoadjuvant therapy in a Jehovah's witness with locally advanced pancreatic cancer: case report and approach to avoid transfusion.

Although the morbidity and mortality rates associated with pancreaticoduodenectomy (PD) have been improving over the past several decades, perioperative transfusions are often needed. Here, we review the preoperative planning and overall management of a Jehovah's Witness patient with locally advanced pancreatic cancer who would not accept blood transfusion. Management of this case is reviewed, along with the relevant literature regarding major surgery in the Jehovah's Witness population. The use of neoadjuvant chemoradiation was used successfully in locally advanced disease, allowing surgical resection. In addition, we outline a cogent strategy using pre-, intra-, and postoperative techniques to minimize blood loss and maintain hemoglobin at acceptable levels thereby preventing the need for transfusion. These strategies, once in place, may be able to reduce transfusions in all patients having major resections for malignancy.

Adenocarcinoma↗
PubMed2003

Neoadjuvant therapy for high-risk localized prostate cancer.

Prostate cancer patients with clinical stage T3 disease, biopsy Gleason scores of 8 to 10, or serum prostate-specific antigen levels greater than 20 ng/mL are at high risk of recurrence despite local therapy. Although hormonal therapy has palliative benefit for the majority of patients with metastatic disease, randomized trials have not demonstrated a survival benefit for its administration prior to surgery for locally advanced disease. Historically, chemotherapy has been felt to have little activity in hormone-refractory prostate cancer, but new evidence may refute this belief. Ongoing clinical trials are now investigating the use of chemotherapy in the neoadjuvant setting. We review the recent literature regarding the use of neoadjuvant hormonal manipulation, chemotherapy, and promising new molecular targeted agents in patients with high-risk localized prostate cancer.

Antineoplastic Agents, Hormonal↗
PubMed2002

Neoadjuvant therapy before radical prostatectomy for clinical T3/T4 carcinoma of the prostate: 5-year followup, Phase II Southwest Oncology Group Study 9109.

PURPOSE: Several investigators have examined the role of hormonal therapy before definitive local therapy for locally advanced prostate cancer to improve outcome. We evaluated the resectability rate and clinical response rate to 16 weeks of total androgen blockage therapy for clinically locally prostate cancer before radical prostatectomy, and progression-free survival in this multi-institutional study. MATERIALS AND METHODS: Southwest Oncology Group 9109 was a phase II feasibility study designed to treat patients with clinical stage C prostate cancer (T3, T4, N0 and M0). Cases were classified by stage T3 versus T4 and bulky (greater than 4 cm.) versus nonbulky (or less 4 cm.) disease. The neoadjuvant agents used were goserelin and flutamide before radical prostatectomy. RESULTS: A total of 62 patients were accrued to the study and 1 patient was ineligible. There were 2 protocol deviations and these patients refused to undergo prostatectomy after hormonal therapy. Four patients went off protocol treatment because they were not considered surgical candidates. The racial distribution was 72% white, 20% black, 7% Hispanic and 2% Asian. Clinical stage at diagnosis was T3 in 97% and T4 in 3% of cases. Of the patients 39% were diagnosed with bulky disease. Of the 61 eligible patients 55 (90%) underwent a prostatectomy. The 5-year progression-free survival estimate was 70% (24 of 61 cases failed) and the 5-year survival estimate was 90% (11 of 61 deaths). Most of the patients in this trial would have been considered inoperable and referred to radiation oncology. CONCLUSIONS: Neoadjuvant hormonal therapy followed by radical prostatectomy is reasonable and appropriate for clinical stage T3 prostate cancer. A progression-free and overall 5-year survival of 70% and 90%, respectively, compares favorably to Radiation Therapy Oncology Group neoadjuvant trial outcomes for this stage of prostate cancer.

Aged↗
PubMed2002

Predictive factors for response to neoadjuvant therapy in patients with oesophageal cancer.

BACKGROUND: Preoperative radio-chemotherapy (RCX) was introduced to improve the outcome of patients with oesophageal cancer (EC), but conflicting results have been released. Some 20-30% of patients show a complete pathological response, however, the perioperative morbidity and mortality is increased. To search for factors indicating response prior to the onset of RCX we investigated the proliferative activity (MIB-1), the expression of vascular endothelial growth factor (VEGF), and the capillary density (CD34) in samples of EC obtained by endoscopy prior to the start of the treatment. METHODS: Forty-six (MIB-1) and 21 (VEGF, CD34) tissue specimens of ECs were available from 56 patients undergoing pretherapeutic endoscopy, RCX and surgery. Perioperative morbidity was divided into surgery and non-surgery related morbidity. MIB-1, VEGF and CD34 expression were investigated immunohistochemically. Multivariate analysis was carried out to prove independence of investigated variables. RESULTS: Postoperative morbidity was noticed in 54 of 56 operated patients. Eight of 56 patients who received RCX died in hospital. Survival was significantly different between the group of complete responders (n=14) and non-responders (n=23; P=0.0026). None of the investigated tumour samples from patients with a complete response (CR) had a proliferation index of less than 45. Tumour samples from patients with a CR showed a VEGF expression of 10.7 compared with 36.58 of tumours with no response (P=0.035). CD34 expression showed a correlation with VEGF expression. The relation of mean indices of VEGF expression and proliferative activity in tumours from patients with complete, partial or no response was 10.7:58.8, 18.3:53.8 and 36.6:43.5, respectively. CONCLUSIONS: According to these results, it may be expected that tumours with a VEGF/MIB-1 ratio of 1:6 or less prior to RCX will respond to this therapy.

Adenocarcinoma↗
PubMed2000

Antiaromatase agents: preclinical data and neoadjuvant therapy.

Novel drugs such as exemestane are highly potent and specific inactivators of aromatase activity in test systems such as placental microsomes, breast cancer homogenates, and cultures of mammary fibroblasts, with IC50 values in the nmol range. When given in daily milligram amounts to postmenopausal women, exemestane almost totally blocks peripheral aromatase and reduces circulating estrogens to levels that are at the limit of detection of current assays. Additionally, exemestane profoundly inhibits in situ aromatase activity both in breast cancers and surrounding nonmalignant breast. In postmenopausal women with large estrogen receptor-rich cancers, these endocrine influences translate into antitumor effects, and, for example, following exemestane treatment in the neoadjuvant setting, tumor resolution may be observed on mammography. In conclusion, the ability to block estrogen biosynthesis peripherally and locally within the breast provides new options for the treatment of hormone-sensitive breast cancers in postmenopausal women

Aromatase Inhibitors↗
PubMed2004

Neoadjuvant therapy and biliary decompression lower biliary and pancreatic juice vascular endothelial growth factor levels in patients with periampullary adenocarcinoma.

Increased expression of vascular endothelial growth factor (VEGF) by pancreatic cancer correlates with poor survival. The significance of VEGF in biliary and pancreatic secretions in periampullary cancers is unknown. Bile and pancreatic juice samples were collected from patients undergoing pancreaticoduodenectomy (PD). All samples were frozen at -70 degrees C until subsequent analysis for VEGF concentration using enzyme-linked immunoabsorbent assay (ELISA). Plasma VEGF levels in pancreatic cancer patients were <10 pg/mL. The biliary VEGF concentration for patients with malignancy was significantly elevated compared to benign disease (P = 0.05). There was no difference in pancreatic VEGF concentrations between benign and malignant disease. Cancer patients undergoing preoperative chemoradiation (CRT) had lower biliary and pancreatic VEGF concentrations than those who did not. Preoperative biliary drainage (BD) was associated with decreased VEGF concentrations in bile (3500 pg/mL vs 7740 pg/mL, P = 0.027). Patients undergoing both CRT and BD had diminished biliary and pancreatic VEGF concentrations compared to those who had neither. This was statistically significant for pancreatic VEGF concentrations (917 pg/mL vs 4723 pg/mL, P = 0.044). VEGF is highly concentrated in bile and pancreatic juice compared to plasma. Preoperative CRT and BD significantly reduce these levels in patients with periampullary cancers. Antiangiogenic therapy aimed at interrupting the VEGF pathway appears to be a logical target in periampullary cancer.

Adenocarcinoma↗
PubMedDate not supplied

Neoadjuvant therapy of rectal cancer new treatment perspectives.

During the past two decades, significant advances have been made in the management of patients with rectal cancer. A number of clinical studies have demonstrated the efficacy of preoperative chemoradiation therapy with 5-fluorouracil (5-FU)-based regimens in decreasing local recurrences and improving survival and the likelihood of sphincter preservation. Although 5-FU has been the standard drug used in combination with radiation therapy for many years, new effective drugs including capecitabine, raltitrexed, irinotecan and oxaliplatin have been recently investigated in combination with radiation therapy in the preoperative setting. In addition, novel targeted biological agents including epidermal growth factor receptor inhibitors and vascular endothelial growth factor inhibitors have been shown to enhance the antitumor effect of both radiation and chemotherapy and are currently being explored in initial clinical trials. In the present review we summarize the results of adjuvant therapy. In addition, we will discuss the recently reported phase I-II trials with new drug plus radiation combinations in the preoperative treatment of patients with rectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗