[Neoadjuvant hormone therapy before prostatectomy for cancer localized to the prostate].
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Androgen Antagonists↗
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Results for “Neoadjuvant therapy”
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Proceedings of the 1st International Conference on Neoadjuvant Hormonal Therapy for Prostate Cancer. Boston, Massachusetts, March 29-30, 1996.
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Androgen Antagonists↗
Assessment of prostate cancer volume using endorectal coil magnetic resonance imaging: a new predictor of tumor response to neoadjuvant androgen suppression therapy.
OBJECTIVES: A clinical tool that can reliably assess prostate cancer response to androgen suppression is lacking. This pilot study was designed to identify the potential clinical factor(s) that correlate with tumor response after neoadjuvant therapy. METHODS: Twenty-one patients managed with definitive local therapy and neoadjuvant androgen suppression (median 3 months [range 2 to 7]) between 1995 and 1997 comprise the study population. Fisher's exact test was used to test the significance of the proportion of patients with a given clinical factor and the outcome of pathologic organ-confined disease. The clinical factors tested included preoperative prostate-specific antigen, biopsy Gleason score, clinical stage, months of total androgen suppression, the change in the endorectal magnetic resonance imaging (erMRI)-defined stage, the change in erMRI-defined tumor, and the change in the erMRI-defined prostate volume during neoadjuvant androgen suppression. RESULTS: All 21 patients had a decrease in the erMRI-determined prostate volume and prostate-specific antigen during androgen suppression, whereas only 10 of 21 (48%) had a reduction in the erMRI-determined tumor volume. There was a statistically significant increased proportion of patients with a decrease in the erMRI-determined tumor volume (P = 0.008) who had pathologic organ-confined disease. CONCLUSIONS: The results of this pilot study suggest that the changes in the erMRI-determined tumor volume occurring during androgen suppression may be predictive of the tumor response. Validation in a larger prospective study is currently underway.
Androgen Antagonists↗
Aromatase inhibitors in early breast cancer therapy.
Third-generation aromatase inhibitors, letrozole, anastrozole, and exemestane, are active and well tolerated in postmenopausal patients with hormone-sensitive advanced or metastatic breast cancer, as either first- or second-line therapy. These agents are being investigated as neoadjuvant therapy of locally advanced breast cancer and as adjuvant therapy of early breast cancer. In a large neoadjuvant study, letrozole resulted in significantly more responses than tamoxifen, with significantly more patients becoming eligible for breast-conserving surgery. Greater letrozole responses were associated with high and low levels of estrogen receptor expression and with coexpression of ErbB-1 and/or ErbB-2. Neoadjuvant anastrozole, in two studies, was also significantly superior to tamoxifen in rendering patients eligible for breast-conserving surgery. In the adjuvant setting, the Arimidex, Tamoxifen Alone or in Combination trial compared 5 years of anastrozole versus tamoxifen versus the combination. At 47 months' median follow-up, disease-free survival was significantly improved with anastrozole compared with the other arms. In the Intergroup Exemestane Study, switching to exemestane after 2 to 3 years of tamoxifen significantly improved disease-free survival compared with remaining on tamoxifen for 5 years. The MA.17 trial evaluated switching to letrozole versus placebo following 5 years of adjuvant tamoxifen, and letrozole was significantly superior to placebo in disease-free survival. While all three aromatase inhibitors as adjuvant therapy were well tolerated, long-term effects on bone health and lipids are being monitored. Ongoing trials will better define the optimum use of aromatase inhibitors as adjuvant therapy.
Antineoplastic Agents↗
Rectal cancer: review with emphasis on MR imaging.
One concern after rectal cancer surgery is the high local recurrence rate. Randomized trials have shown that the best local control rate for rectal cancer patients as a group is achieved after a short course of radiation therapy followed by optimal surgery. It is debatable, however, whether all patients with rectal cancer should undergo preoperative radiation therapy. Preoperative identification of those most likely to benefit from neoadjuvant therapy is important. Therefore, the challenge for preoperative imaging in rectal cancer is to determine subgroups of patients with different risks for recurrence: those with superficial tumors, who can be treated with surgery alone; those with operable tumors and a wide circumferential resection margin, who can be treated with a short course of radiation therapy followed by total mesorectal excision; and those with advanced cancer and a close or involved resection margin, who require a long course of radiation therapy, with or without chemotherapy, and extensive surgery. So far, there is no consensus on the role of diagnostic imaging (endorectal ultrasonography, computed tomography, and magnetic resonance [MR] imaging) in the care of patients with primary rectal cancer. Preoperative staging has long relied on digital examination alone, which indicates that it has been difficult to achieve accuracy levels high enough for clinical decision making with preoperative imaging. In this review, the relevance of preoperative imaging in staging the local extent of primary rectal cancer will be discussed. Research on various imaging modalities, with an emphasis on MR, will be discussed under four main headings that address the most relevant aspects of local spread of rectal tumors: T stage, circumferential resection margin, locally advanced rectal cancer, and N stage.
Combined Modality Therapy↗
Management of high-risk localized prostate cancer: the integration of local and systemic therapy approaches.
Using a combination of PSA, Gleason score, and clinical stage, it is possible to identify a group of patients with prostate cancer who have a high risk of relapse following initial treatment (e.g., radiotherapy or radical prostatectomy). For these patients, multi-modal therapy may result in improved outcomes. We reviewed published literature to identify methods to identify high-risk patients as well as options for adjuvant or neoadjuvant therapy to reduce risk of disease recurrence. At the present time, the most promising adjuvant therapy is hormonal therapy following radiotherapy for locally advanced disease (T3-T4, or N1). In phase III trials in these patients, survival is improved. For all other applications, including adjuvant and neoadjuvant hormonal therapy, chemotherapy, or radiotherapy, the benefits are unclear. Perhaps most promising at this time, and the subject of a current phase III trial, is the utility of adjuvant chemotherapy in high-risk patients. It will be through the conduct of phase III trials that the benefits of multi-modal therapy will be evaluated. Patients with high-risk prostate cancer undergoing radiotherapy or surgery should be offered participation in these clinical trials.
Adenocarcinoma↗
Anti-aromatase agents in the treatment and prevention of breast cancer.
Anti-aromatase agents now have a central role in the management of breast cancer in postmenopausal women; they are superior to megestrol acetate as second-line therapy and to tamoxifen for initial therapy of metastatic disease. They also are highly active as neoadjuvant therapy. Two classes of anti-aromatase agents are available: steroidal (eg, exemestane) and nonsteroidal (eg, anastrozole, letrozole). Although both types of agents act on the aromatase enzyme, they do so by different mechanisms and have different effects on cellular aromatase activity. Nonsteroidal agents are associated with increased aromatase enzyme content and steroidal agents are associated with decreased content. The increase in aromatase content seen with the nonsteroidal agents may in part explain the development of resistance with these agents and the ability of the steroidal agent exemestane to induce a response when nonsteroidal agents fail. Because the anti-aromatase agents almost completely eliminate endogenous estrogen production, they not only affect breast cancer tissues, but also may alter the function of other estrogen-responsive tissues. However, preclinical data show that the steroidal agent exemestane may actually improve bone and lipid metabolism. In addition, no increase in clinical fracture rate has been noted in women treated with exemestane in metastatic trials; the fracture risk has not yet been studied following prolonged exposure in healthy women. Exemestane associated beneficial effects on these end organs may be due to the steroidal nature of both the parent compound and its principal metabolite, 17-hydroexemestane. Similar benefits have not been reported with nonsteroidal antiaromatase agents. Based on their excellent activity in the metastatic setting, anti-aromatase agents are now being evaluated in the adjuvant setting and in pilot studies for chemoprevention. These studies will provide long-term data in healthy women and will help to differentiate anti-aromatase agents, in terms of their efficacy in the treatment of breast cancer and their effects on end organs.
Anastrozole↗
Successful neoadjuvant synchronous chemo- and radiotherapy for disseminated primary intracranial choriocarcinoma: case report.
We report a 17-year-old male with disseminated intracranial choriocarcinoma at the basal ganglia whose consciousness level was very low at diagnosis. He received neoadjuvant therapy (NAT) consisting of combined chemo- and radiotherapy prior to radical excision of the tumor. Postoperatively he was treated with three courses of high-dose chemotherapy (carboplatin (CBDCA), methotrexate (MTX), and etoposide (VP-16)) and peripheral blood stem-cell transplantation. This combination of therapies resulted in tumor regression on MRI and remarkable improvement in his neurological condition. Ours is the first report of the effectiveness of NAT followed by radical surgery in a patient with disseminated primary intracranial choriocarcinoma.
Adolescent↗
Pathological and molecular predictors of the response of rectal cancer to neoadjuvant radiochemotherapy.
AIMS: The prediction of sensitivity and resistance to neoadjuvant therapy has great potential value for many tumour sites. A neoadjuvant regimen is increasingly the gold standard in rectal cancer management and the aim of this review was to highlight predictive markers currently assessed and evaluate their clinical utility. METHODS: A systematic search of Medline was conducted using the following keywords 'colorectal', 'neoadjuvant', 'molecular', 'predict' and 'radiotherapy'. Original manuscripts from all relevant listings were sourced. These were hand searched for further articles of relevance. RESULTS: Conventional indices including tumour stage and grade were unable to predict histological response. Immunohistochemical assessment of P53 gene, Bcl 2, Bax and microsatellite instability are of no predictive value. Studies utilising molecular response predictors from archival pre-treatment tumour tissues have identified several promising predictive markers including p21, spontaneous apoptosis and direct sequencing of the p53 gene. Global gene expression from fresh pre-treatment tissue using cDNA microarray has only recently been assessed but identified expression differences between 54 genes and was able to predict response with 78% sensitivity and 86% specificity. CONCLUSIONS: Currently there are no clinically useful predictors of response based on standard pathological assessment and immunocytochemistry. Direct gene sequencing of p53, studies of apoptosis and global gene sequencing may hold promise.
Biomarkers, Tumor↗
[Value of radiotherapy and chemotherapy in treatment of operable cancers of the esophagus].
Radiotherapy and chemotherapy have been used for more than twenty years as adjuvant treatment of operable cancer of the esophagus. The palliative effect of adjuvant (or neoadjuvant) radio- and/or chemotherapy has been demonstrated in numerous randomized trials. The purpose of this review is to present the principal randomized trials conducted in the treatment of operable cancer of the esophagus. Alone, radiotherapy does not significantly improve survival in patients with operable cancer of the esophagus, irrespective of the pre- or postoperative timing (three trials and one meta-analysis for preoperative, three trials for postoperative, and one trial for pre- and postoperative radiotherapy). Likewise, alone chemotherapy does not significantly improve survival whether given preoperatively (four trials), postoperatively (two trials) or pre- and postoperatively (one trial). Radiochemotherapy combinations appear to provide more hope, but preliminary results are insufficient to draw a clear conclusion. Nevertheless, trial comparing radiotherapy results with chemotherapy, conducted pre- or postoperatively (four trials) appear to demonstrate a significant effect of chemotherapy. The two trials using neoadjuvant therapy have been conducted on patients with adenocarcinomas of the cardia and/or the lower esophagus and have demonstrated very encouraging results for a small number of patients. Finally, the Herslovic trial, while conducted in patients who were initially inoperable, is the only one which has demonstrated superiority of radiochemotherapy over radiotherapy alone. In conclusion, there is still much room for improvement in survival using combined radio- and chemotherapy with different forms (new agents, new associations) and treatment modes (pre- and postoperative or postoperative alone). Despite the wide use of radiotherapy and chemotherapy for cancer of the esophagus, it must be recalled that surgical resection remains the method providing the best chances of survival.
Carcinoma, Squamous Cell↗
Multimodality Therapy for Esophageal Cancer.
Adjuvant and neoadjuvant therapeutic principles have in recent years received increasing attention in the management of patients with esophageal cancer. A series of randomized prospective trials has convincingly demonstrated that adjuvant postoperative radiation or chemotherapy does not result in a survival advantage after a complete tumor resection. The available data on the role of neoadjuvant preoperative therapy in patients with adenocarcinoma or squamous cell carcinoma of the esophagus are not yet conclusive. While neoadjuvant therapy may undoubtedly reduce the tumor mass in a substantial portion of patients, a series of randomized controlled trials has shown that compared with primary resection, a multimodal approach does not result in a survival benefit in patients with locoregional, i.e., potentially resectable, tumors. In contrast, in patients with locally advanced tumors, i.e., tumors in which a complete tumor removal with primary surgery appears unlikely, neoadjuvant therapy allows a marked downstaging of the primary tumor and thus significantly increases the chance for complete tumor removal on subsequent surgery. However, only patients with objective clinical or histopathological response to preoperative therapy appear to benefit from this approach. Compared with preoperative chemotherapy alone, combined radiochemotherapy increases the rate of response but may also increase postoperative morbidity and mortality. Neoadjuvant therapy should therefore currently be performed only in experienced centers within the context of clinical trials. The identification of factors which would facilitate prediction of the response to neoadjuvant therapy is currently the focus of several studies. Furthermore, more effective and less toxic preoperative therapy regimens are required to increase the response rates and combat systemic recurrences.
Journal Article↗
[Value of local surgical therapy for rectal cancer. A literature analysis].
BACKGROUND: Local excision of pT(1) rectal cancer is recognized as curative treatment, whereas the indication is not clarified for pT(2)-tumours. In addition the prognostic histological analysis criteria and the influence of adjuvant and neoadjuvant measures are open. METHOD: Starting form the publication date 1990 investigations on the local excision, with and without adjuvant or neoadjuvant therapy, were included in our literature search and analysed if they comprised at least 30 patients and a follow up of at least 24 months. We studied the assessment criteria local recurrence, survival rate, histological grading, and the conditions of resection margins. RESULTS: After complete resection of "low grade" rectal cancers local recurrences are expected for the pT(1)-category of mean 8 % and for pT(2)-tumours of mean 22%. Poor differentiated pT(1)-tumours exhibit after complete resection over 18 % and after incomplete, despite adjuvant radio (chemo)-therapy, up to 26% recurrences. For pT(2) "high grade" tumours in mean 50% local recurrences and for pT(2) "low grade" tumours after complete resection and adjuvant irradiation in mean 6% have to be expected. Adjuvant measures cannot lower the local recurrence rate for pT(2) tumours after incomplete resection under 20%. CONCLUSION: Local excision with clear margins represents for pT(1) "low grade" cancer an adequate therapy. Further prospective investigations are necessary to clarify whether adjuvant radio (chemo)-therapy represents a curative therapeutic option for pT(2) "low grade" tumours after complete resection.
Carcinoma in Situ↗
Management of malignant pineal germ cell tumors with residual mature teratoma.
OBJECTIVE: The treatment of intracranial mixed germ cell tumors presents a unique challenge, since eradication of malignant tumor by radiation and/or chemotherapy may spare the benign tumor component. We reviewed our surgical experience with residual malignant pineal germ cell tumors after neoadjuvant therapy. METHODS: Between 1987 and 1997, 16 patients with malignant intracranial germ cell tumors were treated at the Mayo Clinic with a protocol of neoadjuvant chemotherapy and radiation therapy. After the diagnosis was confirmed by histopathological examination, all patients were treated with four cycles of etoposide and cisplatin as well as external beam radiation therapy (range, 3030-5940 cGy). Six patients had an incomplete response to therapy, as demonstrated by observation of residual tumor on magnetic resonance imaging scans. Initial pathology in these six patients was germinoma in four and combinations of yolk sac tumor, embryonal carcinoma, malignant teratoma, and germinoma in two. Two patients had synchronous pineal and suprasellar tumors, with leptomeningeal dissemination. Tumor markers were elevated in four of the six patients at presentation. RESULTS: All patients with residual pineal tumors underwent surgical resection via an infratentorial, supracerebellar approach. Pathological examination revealed mature teratoma in five patients and amorphous debris in one patient. No patient had recurrent malignancy. Significant neurological morbidity occurred in one patient, with no mortality. At a mean follow-up of 23 months, no recurrence on magnetic resonance imaging has been documented. CONCLUSION: Residual pineal tumor occurring after treatment of malignant intracranial germ cell tumor with neoadjuvant therapy is likely to be mature teratoma. Operative resection of these benign recurrences is safe and effective.
Adolescent↗
[Therapeutic management of intra-abdominal and retroperitoneal soft tissue sarcomas].
In this article, we review the diagnostics, therapy, follow-up, and prognosis of intra-abdominal and retroperitoneal soft tissue sarcomas. There are descriptions and discussion of the surgical techniques, advantages and disadvantages of various types and combinations of adjuvant and neoadjuvant therapies, therapy in case of nonresectability, and procedures for desmoid tumors. Further, treatment results, control methods, and studies on new therapeutic approaches are presented.
Abdominal Neoplasms↗
Concurrent paclitaxel and thoracic irradiation for locally advanced esophageal cancer.
Esophageal cancer is a major cause of morbidity and mortality worldwide. Although patients often present with apparently resectable disease, systemic spread frequently occurs before the development of symptoms and detection of tumor. The use of combined chemoradiation therapy, particularly before resection, appears to prolong survival and increase cure rates in certain histologic subtypes. Four randomized phase III trials compared preoperative chemoradiotherapy plus surgery with surgery alone. In trials including only patients with squamous histology, no improvement in survival was observed with preoperative chemoradiation therapy; however, in a trial including only patients with adenocarcinoma histology, improved median and overall survival were observed. Paclitaxel has been evaluated as a single agent in a phase II trial in previously untreated patients with locally advanced unresectable or metastatic esophageal cancer; the overall response rate was 32% and median survival was 13.2 months. Paclitaxel-based combinations also have been evaluated in esophageal cancer; particularly encouraging preliminary results have been achieved with paclitaxel/cisplatin/5-fluorouracil. Because paclitaxel is a potent radiosensitizer, it also has been evaluated in combination with radiation therapy for esophageal and other thoracic cancers, alone and in combination with other chemotherapeutic agents. Preliminary results suggest that neoadjuvant therapy with paclitaxel-based combinations (including 5-fluorouracil and cisplatin) and radiation is highly active, with variable toxicity. A goal of future trials is to assess paclitaxel-based combined modality therapy in combination with other new chemotherapeutic agents.
Antineoplastic Agents, Phytogenic↗
Neoadjuvant and adjuvant therapy for rectal cancer.
The currently available evidence from randomized clinical trials clearly supports the use of adjuvant therapy in general and preoperative combined modality therapy in particular as effective means of decreasing the rates of local recurrence, improving sphincter preservation rates, and probably im-proving overall survival when managing patients with locally advanced adenocarcinomas of the lower two thirds of the rectum. A radical surgical approach with adequately performed, sharp TME remains the standard of care for those patients. There is clearly a need to develop and validate surrogate biomarkers for the identification of patients who respond favorably to preoperative treatment. There is still a significant fraction of rectal cancer patients who ultimately die from their disease. The armamentarium of avail-able therapies is evolving rapidly, and hopefully local control rates and overall survival of rectal cancer patients will continue to improve in the near future.
Adenocarcinoma↗
Monitoring of response to pre-operative chemoradiation in combination with hyperthermia in oesophageal cancer by FDG-PET.
PURPOSE: To evaluate the use of positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) to assess early response to pre-operative chemoradiation therapy in combination with external locoregional hyperthermia in patients with oesophageal cancer by correlating the reduction of metabolic activity with histopathologic response. MATERIAL AND METHODS: Twenty-six patients with histopathologically proven intra-thoracic oesophageal cancer (with < or =2 cm gastric involvement), scheduled to undergo a 5-week course of pre-operative chemoradiation therapy and hyperthermia, were included. FDG-PET was performed before (n = 26) and 2 weeks after initiation of therapy (n = 17). FDG uptake was quantitatively assessed by standardized uptake values. RESULTS: After neoadjuvant therapy, 24 of the 26 patients underwent surgery. In 16 patients changes in FDG uptake were correlated to histopathologic response. In these patients, histopathologic evaluation revealed less than 10% viable tumour cells in eight patients (responders) and more than 10% viable tumour cells in eight patients (non-responders). In responders, FDG uptake decreased by a median -44% (-75 to 2); in non-responders, it decreased by a median of -15% (-46 to 40). At a threshold of 31% decrease of FDG uptake compared with baseline, sensitivity to detect response was 75%, with a corresponding specificity of 75%. The positive and negative predictive values were both 75%. CONCLUSION: FDG-PET is a promising tool for early response monitoring in patients undergoing chemoradiation therapy in combination with hyperthermia.
Adult↗
[Fundamentals and results of cytostatic chemotherapy in some of the most common solid tumors].
In this review we discuss established cytostatic chemotherapies as well as developments and perspectives for the three most common tumour entities. Adjuvant and neoadjuvant therapy models for primary breast cancer are discussed, established and newer concepts in palliative care presented and open questions about high dose chemotherapy raised, which need to be settled before their routine use. Developments in the field of lung cancer therapy such as adjuvant and neoadjuvant approaches are pointed out and the importance of multimodal and interdisciplinary treatment modalities is underlined. Newer cytostatic drugs are compared with established agents. In the field of colorectal cancer several new thymidilatsynthase-inhibitors as well as drugs with different mode of action are available. With these new agents, [table: see text] cytostatic therapy of advanced stages and most probably also in the adjuvant setting could markedly be improved.
Antineoplastic Agents↗