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The optimal management of locally advanced, Stage IIIA NSCLC with N2 level nodal metastases remains challenging and controversial. A number of treatment regimens have been shown safe and effective, but existing clinical trial data frequently falls short of providing guidance to match the right approach with the right patient. We review recent literature in this area and its impact., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The purpose of this article is to update our previous work on the treatment and follow-up in early breast cancer. In this new version we have classified a treatment by immunohistochemistry subtypes of breast cancer. Latest advances in the management of this disease have been compiled, either in the adjuvant and neoadjuvant setting or chemotherapy and hormonal treatment. This review is presented in an easy way for oncologist, fellows and for other specialties.

In this updated SCLC guidelines the authors have reviewed the "SEOM recommendation" for diagnosis and treatment of patients, including consideration for elderly and unfit patients. We hope the SCLC guidelines will be useful for residents and oncology teams.

Surgical resection remains the standard of care for clini- cally localized renal cell carcinoma (RCC). Nearly 1 in 4 patients will have a recurrence after surgery performed with curative intent, and stand to benefit from additional therapy. Currently, no proven adjuvant or neoadjuvant therapies are available. A number of phase 3 adjuvant therapy trials are ongoing that are evaluating small-molecule drugs approved for metastatic RCC. The outcomes of these trials may provide insights for designing future phase 3 neoadjuvant therapy trials. Several phase 2 neoadjuvant trials for RCC have recently been completed or are ongoing. These trials have established the safety and response rates associated with several agents, and will pave the way for future phase 3 trials of neoadjuvant therapy for RCC. Neoadjuvant therapies may be useful for decreasing the risk of recurrence after surgery, maximiz- ing nephron sparing, and evaluating molecular effects of targeted therapies in human tumors.

Context: The European Association of Urology (EAU) Guidelines Group on Muscle-Invasive and Metastatic Bladder Cancer prepared these guidelines to deliver current evidence-based information on the diagnosis and treatment of patients with primary urethral carcinoma (UC)., Objective: To review the current literature on the diagnosis and treatment of patients with primary UC and assess its level of scientific evidence., Evidence Acquisition: A systematic literature search was performed to identify studies reporting urethral malignancies. Medline was searched using the controlled vocabulary of the Medical Subject Headings database, along with a free-text protocol., Evidence Synthesis: Primary UC is considered a rare cancer, accounting for <1% of all malignancies. Risk factors for survival include age, tumour stage and grade, nodal stage, presence of distant metastasis, histologic type, tumour size, tumour location, and modality of treatment. Pelvic magnetic resonance imaging is the preferred method to assess the local extent of urethral tumour; computed tomography of the thorax and abdomen should be used to assess distant metastasis. In localised anterior UC, urethra-sparing surgery is an alternative to primary urethrectomy in both sexes, provided negative surgical margins can be achieved. Patients with locally advanced UC should be discussed by a multidisciplinary team of urologists, radiation oncologists, and oncologists. Patients with noninvasive UC or carcinoma in situ of the prostatic urethra and prostatic ducts can be treated with a urethra-sparing approach with transurethral resection and bacillus Calmette-Guérin (BCG). Cystoprostatectomy with extended pelvic lymphadenectomy should be reserved for patients not responding to BCG or as a primary treatment option in patients with extensive ductal or stromal involvement., Conclusions: The 2013 guidelines document on primary UC is the first publication on this topic by the EAU. It aims to increase awareness in the urologic community and provide scientific transparency to improve outcomes of this rare urogenital malignancy., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Level I evidence supports neoadjuvant chemotherapy in the treatment of advanced bladder cancer. For the most benefit, it is suggested that neoadjuvant chemotherapy be restricted to patients with clinical T3 disease and/or clinical N+ disease., (Copyright © 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

New approaches to drug development are critically needed to lessen the time, cost, and resources necessary to identify and optimize active agents. Strategies to accelerate drug development include testing drugs earlier in the disease process, such as the neoadjuvant setting. The U.S. Food and Drug Administration (FDA) has issued guidance designed to accelerate drug approval through the use of neoadjuvant studies in which the surrogate short-term endpoint, pathologic response, can be used to identify active agents and shorten the time to approval of both efficacious drugs and biomarkers identifying patients most likely to respond. However, this approach has unique challenges. In particular, issues of patient safety are paramount, given the exposure of potentially curable patients to investigational agents with limited safety experience. Key components to safe drug development in the neoadjuvant setting include defining a study population at sufficiently poor prognosis with standard therapy to justify exposure to investigational agents, defining the extent and adequacy of safety data from phase I, detecting potentially harmful interactions between investigational and standard therapies, improving study designs, such as adaptive strategies, that limit patient exposure to ineffective agents, and intensifying safety monitoring in the course of the trial. The I-SPY2 trial is an example of a phase II neoadjuvant trial of novel agents for breast cancer in which these issues have been addressed, both in the design and conduct of the trial. These adaptations of phase II design enable acceleration of drug development by reducing time and cost to screen novel therapies for activity without compromising safety., (©2013 AACR)

Context: We present a summary of the Second International Consultation on Bladder Cancer recommendations on chemotherapy for the treatment of bladder cancer using an evidence-based strategy., Objective: To review the data regarding chemotherapy in patients with clinically localized and metastatic bladder cancer with a focus on its use for patients in the neoadjuvant and adjuvant settings., Evidence Acquisition: Medline databases were searched for original articles published prior to April 1, 2012, using the following search terms: bladder cancer, urothelial cancer, metastatic, advanced, neoadjuvant, and adjuvant therapy. Proceedings of major conferences from the last 5 yr also were searched. Novel and promising drugs currently in clinical trials were included., Evidence Synthesis: The major findings are addressed in an evidence-based manner. Prospective trials and important cohort data were analyzed., Conclusions: Cisplatin-based combination chemotherapy for advanced and metastatic bladder cancer is an established standard, improving overall survival. In the advanced setting, cisplatin-ineligible patients may benefit from gemcitabine and carboplatin. Meta-analyses undertaken for neoadjuvant cisplatin-based combination chemotherapy show a 5% benefit in overall survival. Pathologic complete remission may be an intermediate surrogate for survival, but requires further validation. Use of neoadjuvant chemotherapy is low, and is attributable to patient and physician choice because of limited benefit, advanced age, and comorbidities including renal and/or cardiac dysfunction. Sufficient data to support adjuvant chemotherapy are lacking., (Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Introduction: Radiotherapy has proven to be an effective treatment when used alone or with other therapies. However, underuse of radiotherapy has been observed in various studies. The objective of this investigation was to assess the use of radiotherapy as initial treatment for lung cancer in a southern region of Europe., Methods: A systematic review of lung cancer treatment guidelines and observational studies was performed to estimate expected radiation rates and the associated survival outcomes. We then reviewed the clinical and treatment records of all patients undergoing radiotherapy for lung cancer during 2007 in all the 12 public hospitals in Andalusia with radiotherapy facilities. Data were grouped according to type of hospital, patient, treatment characteristics, histological type, and tumor stage., Results: In 2007, of the 3051 patients estimated to be diagnosed with lung cancer, 610 were treated with initial radiotherapy with an overall radiation rate of 20%, which significantly differed among provinces (range, 8.5%-25.6%, p < 0.001). Given the expected radiation rate of 1383 patients, 773 more patients of lung cancer (25%) should have been treated. According to the literature, the maximum increased survival attributable to the use of radiotherapy in patients diagnosed with non-small-cell lung cancer ranges from 1.8 to 14.1 months. The underuse estimated in the region would correspond to a loss of more than 3000 months in survival time., Conclusions: The observed underuse of radiotherapy in lung cancer in our region should be a matter of concern, given its negative and measurable impact on the survival of the patients.

Gastric cancer and cancer of the gastro-oesophageal junction (GOJ) are the 4th most common cancer diagnoses worldwide with regional differences in incidence rates. The treatment of gastric and GOJ cancers is complex and requires multimodality treatment including chemotherapy treatment, surgery, and radiotherapy. During the past decade considerable improvements were achieved by advanced surgical techniques, tailored chemotherapies/radiotherapy and technical innovations in clinical diagnostics. In patients with advanced or metastatic gastric/GOJ cancer systemic chemotherapy with fluoropyrimidine/platinum-based regimens (+/-human epidermal growth factor receptor-2 antibody) is the mainstay of treatment. Despite these improvements, the clinical outcome for patients with advanced or metastatic disease is generally poor with 5-year survival rates ranging between 5%-15%. These poor survival rates may to some extent be related that standard therapies beyond first-line therapies have never been defined. Considering that this patient population is often not fit enough to receive further treatments there is an increasing body of evidence from phase-2 studies that in fact second-line therapies may have a positive impact in terms of overall survival. Moreover two recently published phase-3 studies support the use of second-line chemotherapy. A South Korean study compared either, irinotecan or docetaxel with best supportive care and a German study compared irinotecan with best supportive care-both studies met their primary endpoint overall survival. In this "Field of Vision" article, we review these recently published phase-3 studies and put them into the context of clinical prognostic factors helping to guide treatment decisions in patients who most likely benefit.

Background: Stage IIIA(N2) non-small cell lung cancer is a heterogeneous spectrum ranging from microscopic lymph node metastases to bulky multistation nodal disease. While some favor surgical resection after neoadjuvant therapy, others favor definitive chemoradiation for treatment. Our aim was to determine practice patterns of thoracic surgeons., Methods: We invited 2,539 active surgeons identified on the Cardiothoracic Surgery Network as expressing interest in general thoracic surgery to participate in an anonymous Web-based survey. The participants evaluated clinical vignettes of a patient with single station N2 disease., Results: In all, 513 surgeons (20%) responded, with 222 (43%) in academic practice. For microscopic N2 disease, 84% (n=430) preferred neoadjuvant therapy followed by surgery. For grossly involved N2 disease, 62% (n=318) favored neoadjuvant therapy followed by surgery if N2 disease was downstaged. In patients with normal pulmonary function tests, requiring pneumonectomy, in the presence of bulky, single station N2 disease, there was less consensus: 32% (n=163) favored neoadjuvant therapy followed by lobectomy (less radical surgery than initially predicted) if feasible and N2 disease had downstaged, 30% (n=159) favored neoadjuvant therapy followed by pneumonectomy if N2 disease downstaged, 12% (n=60) would favor surgery regardless of N2 disease downstaging, and 22% (n=114) favored definitive chemoradiation. If the patient did not have adequate pulmonary function for pneumonectomy but could tolerate lobectomy, 50% favored neoadjuvant therapy followed by reassessment for lobectomy and 41% favored definitive chemoradiation., Conclusions: There is no clear consensus on management of patients with stage IIIA lung cancer in the United States. Diversity of opinion is greatest in patients with more advanced lung cancer, and limited pulmonary function., (Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

The use of neoadjuvant systemic therapy (NST) for the treatment of primary breast cancer has constantly increased, especially in trials of new therapeutic regimens. In the 1980 s, NST was shown to substantially improve breast-conserving surgery rates and was first typically used for patients with inoperable locally advanced or inflammatory breast cancer. Investigators have since also used NST as an in vivo test for chemosensitivity by assessing pathologic complete response. Today, by using pathologic response and other biomarkers as intermediate end points, results from trials of new regimens and therapies that use NST are aimed to precede and anticipate the results from larger adjuvant trials. In 2003, a panel of representatives from various breast cancer clinical research groups was first convened in Biedenkopf to formulate recommendations on the use of NST. The obtained consensus was updated in two subsequent meetings in 2004 and 2006. The most recent conference on recommendations on the use of NST took place in 2010 and forms the basis of this report.

Pediatric surgeons play a critical role in diagnosing, staging, and treating malignant solid tumors in children. Over the years, the surgical management of the primary tumor site has evolved from an aggressive en-bloc resection at diagnosis to a more tailored surgical approach, often affecting definitive local control after the delivery of neoadjuvant therapy, as currently directed by many solid tumor protocols. In fact, inappropriate upfront resection can lead to unnecessary short- and long-term morbidity, an incomplete resection, and may be associated with a delay in the initiation of the systemic chemotherapy that is critical to the treatment of gross or occult metastatic disease. Therefore, it is important for the pediatric surgeon, as a member of the multidisciplinary team involved in the care of these children, to understand the indications for and implications of neoadjuvant therapy in the treatment of pediatric solid tumors. Here we review the current management of childhood solid tumors focusing on the role of neoadjuvant therapy., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Aim: We present an alternative approach to quality assessment in colorectal cancer, enabling a direct comparison of improvement at the level of the care provider., Method: In 2000, a quality assessment project in colorectal cancer in Germany was started. Data were provided for every patient treated for colorectal cancer. The enrolment questionnaire described patient data, risk factors, reason for hospitalization, diagnostics prior to surgery, surgical procedures, intraoperative complications, general and surgical complications in postoperative period, pathological report and discharge status., Results: From 2000 to 2007, there were 57 429 patients included in the study. The total number of 372 hospitals that took part in the project varied from 153 to 281 per year. The overall resection rate for colon cancer was 97.1% and 94.8% for rectal cancer. Although the localization of rectal tumours did not vary, the percentage of abdominoperineal excisions fell from 26.1% in 2000 to 21.3% in 2008 (P < 0.001). Hospital mortality for colon cancer varied between 3.2% and 4.2% (P Pearson chi-square 0.032, linear-by-linear 0.257) and for rectal cancer between 2.7% and 3.7% (P Pearson chi-square 0.233). Patient age was not related to in-hospital mortality., Conclusion: The proposed model of quality assessment shows validity and results comparable to population-based studies. It does not require support from the health care system, making its implementation possible in every hospital worldwide., (© 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.)

There are 2 types of neoadjuvant radiation regimens accepted as standard for resectable rectal cancer: short-course (5 × 5 Gy) radiation therapy alone with immediate surgery and long-course combined chemoradiation therapy with delayed surgery. A Polish randomized study (n = 312) and an Australian randomized study (n = 326) compared these 2 schedules. Both trials showed a lower rate of early adverse effects using a short-course radiation regimen and no differences in long-term oncologic outcomes and late toxicity rates between groups. The small number of fractions makes short-course radiation less expensive and more convenient than chemoradiation therapy. These facts indicate that short-course radiation is preferable to chemoradiation for resectable cancers. Additionally, short-course preoperative radiation with a long interval to surgery is a valuable option for patients unfit for chemotherapy, with unresectable cancer or with a small tumor that is amenable to local excision. Moreover, short-course radiation enables the intensification of both radiotherapy and chemotherapy in patients with metastatic rectal cancer with potentially resectable synchronous metastatic disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

There are 2 approaches to preoperative therapy. Short-course (25 Gy in 5 fractions) radiation and long-course (50.4 Gy in 28 fractions) radiation combined with chemotherapy (CMT). Although short-course radiation therapy is used in some European countries, it is not favored in all European countries or North America. Unlike long-course CMT, it cannot be safely combined with adequate doses of systemic concurrent chemotherapy, and, as currently designed, it does not increase sphincter preservation. Long-course CMT remains the preferred regimen for cT3 and/or node-positive disease. With parallel advances in staging, surgery, systemic therapy, and molecular markers, more selective approaches are being investigated., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Current management of early-stage rectal cancer comprises combinations of surgery, radiotherapy, and chemotherapy, with the presence or absence of several validated high-risk features determining which treatment modalities will be used and the order of administration. In high-risk individuals, most centers have adopted neoadjuvant combined chemotherapy and radiotherapy followed by surgery as the initial approach. However, long-term toxicity, limited survival gains, and high rates of distant failure have called this approach into question, with early data suggesting that neoadjuvant chemotherapy alone may be feasible in selected patient groups. This review discusses the current data and feasibility of managing early stage rectal cancer with neoadjuvant chemotherapy before surgical resection., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A neoadjuvant multimodality approach with chemoradiation therapy (CRT) is the preferred treatment strategy for most distal rectal cancers. Significant downstaging and complete pathologic response may develop after this strategy, and there is still controversy regarding the management of these patients. In this setting, a nonoperative approach has been suggested in select patients with complete clinical response after thorough clinical, endoscopic, and radiologic assessment. However, the assessment of these patients is not straightforward and remains complex. Available data regarding this approach are limited to a single institution's experience from retrospective analyses. Standardization of the assessment of tumor response and the development of radiological/molecular tools may clarify the role of no immediate surgery in patients with complete clinical response after neoadjuvant CRT. Advances in radiation and medical oncology could potentially lead to significant improvements in complete tumor regression rates, leading to an increase in importance of a minimally invasive approach in patients with rectal cancer., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Advanced-stage epithelial ovarian cancer is generally managed with cytoreductive surgery and chemotherapy consisting of carboplatin and paclitaxel, achieving clinical complete remission in the majority of patients. However, most tumors recur, and are associated with progressive chemotherapy resistance. Techniques to optimize chemotherapy have included intraperitoneal administration and weekly scheduling of paclitaxel. Efforts to improve on the long-term results of primary therapy through addition of a third cytotoxic agent have not been successful, including extended maintenance, as well as strategies to overcome chemotherapy resistance. Limited data emerging from phase III trials using bevacizumab suggest some advantage in progression-free survival, particularly in the maintenance setting, and further data are awaited. At present, primary therapy with carboplatin and paclitaxel remains a well-tolerated standard regimen, including the option of weekly paclitaxel dosing, intraperitoneal delivery and neoadjuvant therapy in selected patients. Emerging biological paradigms will hopefully contribute to individualized treatment options in the future.

Pancreatic cancer is one of the most devastating solid tumor malignancies. Majority of patients have metastatic disease upon diagnosis. Five-year survival is less than 5% for all stages of pancreatic cancer combined. Gemcitabine has been the standard palliative therapy for advanced pancreatic cancer over the past decade. Many studies attempted to develop combination regimens, but they failed to improve overall survival in the metastatic settings. The combination of gemcitabine and erlotinib was the first combination regimen to show improvements in survival benefit compared with gemcitabine alone and became the first-line combination therapy in advanced pancreatic cancer. The search for better treatment strategies to prolong survival in this deadly disease is very much needed and is a worldwide effort. There were many studies presented at the 2010 American Society of Clinical Oncology (ASCO) Annual Meeting focused on first-line therapy in metastatic pancreatic cancer. This article highlights a few phase III and II studies that have demonstrated encouraging results.

Background: Colorectal carcinoma (CRC) is the second most common type of cancer in Germany. In view of recent major changes in the diagnosis and treatment of CRC, the S3 guideline for CRC published in its full version in 2004 was partially updated in 2008 and again in 2009., Method: The literature was systematically searched for all articles published from 2004 onward concerning polyp management, (neo-)adjuvant treatment, and treatment of metastatic disease. Evidence-based recommendations were developed in a consensus conference., Results: For some patients who have undergone polypectomy, the time to follow-up with colonoscopy can be lengthened. In UICC stage III colon cancer, adjuvant chemotherapy with an oxaliplatin-based regimen is recommended. In stage II colon cancer, adjuvant chemotherapy should be considered mainly when risk factors are present. In stages II and III, neo-adjuvant therapy should be given before resection in rectal cancer. In patients with metastatic disease, the use of all possible treatment options results in a median overall survival time of 24 months. In some patients with primarily non-resectable liver metastases, systemic treatment may enable a secondary, potentially curative resection. Therapeutic agents are chosen individually on the basis of clinical factors including the goal of treatment, the patient's general condition, and tumor molecular markers., Conclusion: The S3 guideline contains evidence-based recommendations for the diagnosis and treatment of colorectal carcinoma. Broad implementation of the guideline will be essential for improved patient care.

Purpose: A cohort study was carried out to analyse quality indicators in the diagnosis and treatment of rectal carcinoma., Methods: A total of 2,470 patients with rectal carcinoma treated between 1985 and 2007 at the Department of Surgery, University of Erlangen, were analysed and compared within four time intervals., Results: Most of the indicators analysed from 2004 to 2007 fulfilled the defined target values. The indicators for process quality of surgical treatment and the surrogate indicators of outcome quality in surgery showed excellent results. Comparing this to previous data, it displays the new developments such as introduction of multimodal treatment for high-risk patients. While the rate of locoregional recurrences decreased, no significant improvement in survival was found., Conclusions: Careful analysis of quality indicators is important for both quality management and comparison of treatment results. The progress in diagnosis and treatment requires a continuous update of definitions and target values.

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.

As therapy for locoregionally advanced head and neck cancer (HNC) has evolved, treatment has become increasingly aggressive and cure rates have risen. However, survival still remains poor. The evolving standard of care has focused on the concurrent use of chemotherapy with more aggressive radiotherapy; however, patients continue to recur locally and/or regionally, albeit at a diminished rate, and distant metastases have become a major site of fatal recurrence, while long-term local and acute systemic toxicities have increased. As a result of these changes in outcomes and a re-evaluation of earlier historical data by meta-analyses, interest in cisplatin and 5-fluorouracil (PF) induction chemotherapy has re-emerged and evolved. Most recently randomized studies comparing PF with PF plus a taxane, in particular docetaxel (TPF regimen), have demonstrated markedly superior survival with the three-drug regimens. TPF is now considered the standard of care for induction chemotherapy. Induction chemotherapy followed by chemoradiotherapy, known as sequential therapy, has been shown to be safe and effective. This approach is promising and may have a survival advantage over chemoradiotherapy alone. Both TPF induction and sequential therapy are considered appropriate platforms upon which the new molecularly targeted agents can be tested.

Neoadjuvant chemotherapy (NACT) is a term originally used to describe the administration of chemotherapy preoperatively before surgery. The original rationale for administering NACT or so-called induction chemotherapy to shrink or downstage a locally advanced tumour, and thereby facilitate more effective local treatment with surgery or radiotherapy, has been extended with the introduction of more effective combinations of chemotherapy to include reducing the risks of metastatic disease. It seems logical that survival could be lengthened, or organ preservation rates increased in resectable tumours by NACT. In rectal cancer NACT is being increasingly used in locally advanced and nonmetastatic unresectable tumours. Randomised studies in advanced colorectal cancer show high response rates to combination cytotoxic therapy. This evidence of efficacy coupled with the introduction of novel molecular targeted therapies (such as Bevacizumab and Cetuximab), and long waiting times for radiotherapy have rekindled an interest in delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm is currently waning in other sites such as head and neck and nasopharynx cancer where traditionally NACT has been used. So, is NACT in rectal cancer a real advance or just history repeating itself? In this review, we aimed to explore the advantages and disadvantages of the separate approaches of neoadjuvant, concurrent and consolidation chemotherapy in locally advanced rectal cancer, drawing on theoretical principles, preclinical studies and clinical experience both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may improve outcome in terms of disease-free or overall survival in selected groups in some disease sites, but this strategy has not been shown to be associated with better outcomes than postoperative adjuvant chemotherapy. In particular, there is insufficient data in rectal cancer. The evidence for benefit is strongest when NACT is administered before surgical resection. In contrast, the data in favour of NACT before radiation or chemoradiation (CRT) is inconclusive, despite the suggestion that response to induction chemotherapy can predict response to subsequent radiotherapy. The observation that spectacular responses to chemotherapy before radical radiotherapy did not result in improved survival, was noted 25 years ago. However, multiple trials in head and neck cancer, nasopharyngeal cancer, non-small-cell lung cancer, small-cell lung cancer and cervical cancer do not support the routine use of NACT either as an alternative, or as additional benefit to CRT. The addition of NACT does not appear to enhance local control over concurrent CRT or radiotherapy alone. Neoadjuvant chemotherapy before CRT or radiation should be used with caution, and only in the context of clinical trials. The evidence base suggests that concurrent CRT with early positioning of radiotherapy appears the best option for patients with locally advanced rectal cancer and in all disease sites where radiation is the primary local therapy.

In pancreatic cancer, complete resection offers the only hope of cure, but results of surgery alone are suboptimal. Many studies have been conducted in which the treatment regimen consists of surgery in combination with radiation and chemotherapy to improve local control and outcome. Neoadjuvant chemoradiotherapy is a fairly recent approach that appears to be feasible in resectable and locally advanced pancreatic cancer. In resectable tumors, chemoradiation therapy has been shown to be at least as effective in a neoadjuvant setting as in an adjuvant setting. Neoadjuvant therapy offers a few theoretical advantages: (1) beginning the multimodality treatment with chemoradiation therapy increases the chance that more patients will receive all of its components; (2) preoperative chemoradiation therapy provides an observation period to exclude from surgical resection those patients with rapidly progressive disease; and (3) in locally advanced tumors, it provides the opportunity for downstaging and infrequently allows patients to undergo resection. To evaluate the scope and applicability of neoadjuvant treatment, a number of areas need to be addressed. First, the definition of locally advanced disease needs to be more adequately standardized because the resectability definition sometimes varies among surgeons. In addition, because imaging examinations may underestimate the effectiveness of preoperative chemoradiation therapy, some researchers have tried to evaluate treatment response via a pathological examination of the tumor specimen; however, complete pathological response appears to be rare. Finally, more efficient novel neoadjuvant approaches are required to address the high metastatic potential of pancreatic cancer. These areas are discussed in depth.

Combined radiochemotherapy is the recommended standard postoperative therapy for patients with stage II and III rectal cancer in the USA and in Germany. During thelast decade, substantial progress has been made in treatment modalities: surgical management currently includes a broad spectrum of operative procedures ranging from radical operations such as abdominoperineal resections to innovative sphincter-preserving techniques. Specialized groups have reported excellent local control rates with total mesorectal excision (TME) alone without the addition of neoadjuvant or adjuvant treatment. New and improved radiation techniques using conformal radiotherapy as well as innovative chemotherapy schedules and combinations (capecitabine, oxaliplatin, irinotecan) of chemotherapy may have the potential to further increase the therapeutic benefit of (neo-)adjuvant treatment. Moreover, the basic issue of timing of radiotherapy-preoperative versus postoperative-within a multimodality regimen is currently being addressed in prospective trials. Evidently, the current monolithic approach established by studies conducted more than a decade ago, to either apply the same schedule of postoperative radiochemotherapy to all patients with UICC stage II and III rectal cancer or to give preoperative short-course radiation according to the Swedish concept for all patients with resectable rectal cancer irrespective of tumor stage and treatment goal (e.g., sphincter preservation), need to be questioned.

Despite surgical R0 resections, patients with gastric cancer stage UICC II-III have a high risk of recurrence and metachronic metastases. Preliminary evidence exists that adjuvant chemotherapy or neoadjuvant chemo(radio)therapy protocols may improve the prognosis of these patients undergoing surgery of gastric cancer with curative intention. As for palliative regimens, 5-fluorouracil and cisplatin are integral components of such (neo)adjuvant strategies. Upcoming cytostatic agents, i.e. irinotecan, docetaxel, oxaliplatin, and oral fluoropyridines are currently under investigation in new multimodality treatment regimens and may further increase R0 resection rates and may prolong disease-free and overall survival in the treatment of advanced localized gastric cancer., (Copyright (c) 2004 S. Karger AG, Basel.)

While it is now clear that chemotherapy can contribute to improved outcome for some patients with muscle invasive bladder cancer, selection criteria for this very heterogeneous disease are lacking. The authors make an appeal for a biologically (in contrast to anatomically) based staging system, and urge that perioperative chemotherapy be given with standard combinations with curative intent.

The idea of using preoperative or neoadjuvant chemotherapy in patients with operable breast cancer originated from experimental and clinical observations as well as theoretical hypotheses on tumor cell growth and dissemination. Initially, nonrandomized studies demonstrated considerable rates of clinical tumor response, low rates of pathologic complete response (pCR), and increased rates of breast-conserving procedures. However, nonrandomized studies could not address the relative efficacy of neoadjuvant versus adjuvant chemotherapy on disease-free and overall survival. Similarly, earlier randomized trials were not designed as straightforward comparisons of neoadjuvant versus adjuvant chemotherapy and therefore could not adequately address the relative efficacy of neoadjuvant versus adjuvant chemotherapy on outcome. These answers were eventually provided by larger randomized trials that directly compared neoadjuvant with adjuvant chemotherapy, which are reviewed in more detail in this article. Potential advantages and disadvantages of the neoadjuvant approach and surgical considerations in the breast and axilla after neoadjuvant chemotherapy are also discussed. Finally, several recently reported trials of neoadjuvant therapy incorporating newer agents such as taxanes in sequence with anthracycline-containing regimens have shown further increases in pCR rates. Although outcome data are not available yet from these studies, it is hoped that the observed increase in pCR rates will be associated with improved outcome. If the previously observed significant correlation between the achievement of pCR and improved outcome continues to be demonstrated with these newer regimens, it will substantially strengthen the rationale for using neoadjuvant rather that adjuvant chemotherapy in the clinical setting as well as in future research studies.

A systematic review of the literature about the role of chemotherapy in comparison to local therapies--surgery or radiotherapy--in non-small cells lung cancers has identified 35 randomised trials. The methodological assessment has not shown significant difference for quality scores between negative or positive studies in term of survival effect. The aggregation (meta-analysis) shows a significant effect of survival improvement by chemotherapy, whatever all indications are considered or subgroups like adjuvant chemotherapy to surgery, neoadjuvant chemotherapy, concomitant radio-chemotherapy and induction chemotherapy prior to thoracic irradiation.

Interest in platinum compounds for the treatment of breast cancer has been reawakened because of preclinical studies indicating synergy of platinum salts with the monoclonal antibody trastuzumab in human breast cancer cell lines that overexpress HER2/neu. Cisplatin, carboplatin, and iproplatin are not very active as single agents in patients with previously treated metastatic breast cancer (MBC). The activity of oxaliplatin has not been adequately tested in refractory MBC. On the other hand, cisplatin is very active as first-line chemotherapy, with response rates (RR) of 50%; carboplatin appears to be moderately active in patients without prior chemotherapy (RR around 30%). The clinical effectiveness of the other platinum compounds (iproplatin, oxaliplatin, and others) has not yet been fully tested as first-line chemotherapy. Platinum compounds have been extensively tested in combination with other antitumoral agents. Cisplatin combinations have been employed as neoadjuvant chemotherapy in women with locally advanced breast cancer. These combinations are very active, although the precise contribution of cisplatin to the overall activity is not known. Combinations with cisplatin have been investigated, essentially, as salvage therapy for patients with previously treated MBC. The combinations of cisplatin with older pharmacological agents (5-fluorouracil, etoposide) have moderate activity, while the combinations of cisplatin with the newer agents (vinorelbine, paclitaxel, docetaxel, gemcitabine) appear to be more active. The combinations of carboplatin with the classical agents (5-fluorouracil, etoposide) are poorly active in previously treated MBC; however, the combination of carboplatin with the taxanes (docetaxel, paclitaxel) is more active. Of greatest interest is the synergy between the platinum derivatives and the monoclonal antibody trastuzumab demonstrated in vitro in breast cancer cell lines overexpressing HER2/neu. Currently, several combinations of platinum compounds (either cisplatin or carboplatin) with docetaxel and trastuzumab are under clinical testing in patients with MBC who overexpress HER2/neu. The preliminary results are very promising, and these combinations will soon be tested in the adjuvant setting. Cisplatin, carboplatin, and perhaps, oxaliplatin appear to have some antitumor activity in MBC and can be combined safely with other agents that are active in this disease. However, the precise role that platinum compounds play in the treatment of breast cancer remains to be defined.