Factors associated with longer endocrine therapy use by South Carolina Medicaid-insured breast cancer survivors.

PURPOSE: The objective of this study is to determine demographic, clinical, and pharmaceutical factors that are associated with longer endocrine therapy usage duration. METHODS: South Carolina Central Cancer Registry incidence data linked with South Carolina Medicaid prescription claims and administrative data were used. The study included a sample (N = 1399) of female South Carolina Medicaid recipients with hormone receptor-positive breast cancer diagnosed between 2000 and 2012 who filled at least one ET prescription. A series of multiple regression models were built to explore the association of demographic, clinical, and pharmaceutical factors with the endocrine therapy usage duration. RESULTS: Multiple linear regression analysis showed that none of the demographic or clinical factors tested were significantly associated with the endocrine therapy usage duration. However, the type of endocrine therapy taken as well as receipt of the prescriptions that could have been used to alleviate side-effects (adrenals, nonsteroidal anti-inflammatory agents, anti-inflammatory agents, and vitamins) were significantly associated. CONCLUSION: Our study highlights the potential value of concurrent prescriptions for improving the endocrine therapy usage duration, with an optimal intervention point before 14 months post ET initiation. This work informs further research needed to test pharmacologic interventions that may significantly increase the endocrine therapy duration as well as other nonpharmacologic strategies for side-effect management.

Multicentre study of perioperative versus adjuvant chemotherapy for resectable colorectal liver metastases.

Background: It is not known whether perioperative chemotherapy, compared with adjuvant chemotherapy alone, improves disease-free survival (DFS) in patients with upfront resectable colorectal liver metastases (CLM). The aim of this study was to estimate the impact of neoadjuvant 5-fluorouracil, leucovorin and oxaliplatin (FOLFOX) on DFS in patients with upfront resectable CLM. Methods: Consecutive patients who presented with up to five resectable CLM at two Japanese and two French centres in 2008-2015 were included in the study. Both French institutions favoured perioperative FOLFOX, whereas the two Japanese groups systematically preferred upfront surgery plus adjuvant chemotherapy. Inverse probability of treatment weighting (IPTW) and Cox regression multivariable models were used to adjust for confounding. The primary outcome was DFS. Results: Some 300 patients were included: 151 received perioperative chemotherapy and 149 had upfront surgery plus adjuvant chemotherapy. The weighted 3-year DFS rate was 33·5 per cent after perioperative chemotherapy compared with 27·1 per cent after upfront surgery plus adjuvant chemotherapy (hazard ratio (HR) 0·85, 95 per cent c.i. 0·62 to 1·16; P = 0·318). For the subgroup of 165 patients who received adjuvant FOLFOX successfully (for at least 3 months), the adjusted effect of neoadjuvant chemotherapy was not significant (HR 1·19, 0·74 to 1·90; P = 0·476). No significant effect of neoadjuvant chemotherapy was observed in multivariable regression analysis. Conclusion: Compared with adjuvant chemotherapy, perioperative FOLFOX does not improve DFS in patients with resectable CLM, provided adjuvant chemotherapy is given successfully.

Antecedentes: Se desconoce si la quimioterapia perioperatoria en comparación con la quimioterapia adyuvante sola mejora la supervivencia libre de enfermedad (disease­free survival, DFS) en pacientes con metástasis hepáticas de origen colorrectal (colorectal liver metastases, CLM) resecables de inicio. El objetivo de este estudio fue estimar el impacto de la neoadyuvancia con 5­fluorouracilo, leucovorina y oxaliplatino (FOLFOX) sobre la DFS en pacientes con CLM resecables desde el principio. Métodos: Se incluyeron pacientes consecutivos que presentaban hasta cinco CLM resecables en dos centros japoneses y dos centros franceses entre 2008 a 2015. Ambas instituciones francesas favorecían FOLFOX perioperatorio, mientras que los dos grupos japoneses utilizaban sistemáticamente la cirugía de entrada y quimioterapia adyuvante. Se utilizaron la probabilidad inversa del tratamiento ponderado (Inverse Probability of Treatment Weighting, IPTW) y el modelo multivariable de regresión de Cox para ajustar por factores de confusión. El resultado primario fue la DFS. Resultados: Se incluyeron 300 pacientes (grupo de quimioterapia perioperatoria n = 151 y grupo de cirugía de entrada más quimioterapia adyuvante n = 149). La DFS a los 3 años ponderada fue del 33% después de quimioterapia perioperatoria versus 27% tras cirugía de entrada (cociente de riesgos instantáneos, hazard ratio HR: 0,85; i.c. del 95% (0,62­1,16); P = 0,32). Cuando se consideró el subgrupo de pacientes que (n = 165) de manera efectiva (al menos 3 meses) recibieron FOLFOX adyuvante, el efecto ajustado de la quimioterapia neoadyuvante no fue significativo (HR: 1,19 (0,74­1,90); P = 0,48). No se observó un efecto significativo de la quimioterapia neoadyuvante en el análisis de regresión multivariable. Conclusión: En comparación con la quimioterapia adyuvante, el FOLFOX perioperatorio no mejora la DFS en CLM resecables siempre y cuando la quimioterapia adyuvante se administre de forma efectiva.

From VA Larynx to the future of chemoselection: Defining the role of induction chemotherapy in larynx cancer.

Organ preservation protocols utilizing induction chemotherapy as a selection agent have played a critical role in the treatment of advanced laryngeal squamous cell carcinoma (LSCC). The selection of patients who will have a good response to chemoradiation allows for organ preservation in a significant group of patients and minimizes the rate of surgical salvage. While there remains debate regarding its utility when compared to surgery or other organ preservation regimens, the data does suggest an important role for induction chemotherapy in LSCC. In addition, there are continued opportunities to identify pretreatment biomarkers for induction chemotherapy, whether genetic, epigenetic or cellular, that could predict response to treatment and select patients to therapy (whether organ preservation or surgery). As our understanding of the biology of larynx cancer advances, induction paradigms have utility for the development and adoption of novel agents and therapeutics. The background of induction chemotherapy as a selection agent and future directions of this approach are discussed.

Systemic adjuvant therapy for renal cell carcinoma: Any hope for future clinical trials?

The role of adjuvant therapy for renal cell carcinoma (RCC) after surgical resection has been evaluated in numerous randomized and nonrandomized studies using systemic therapies with distinct mechanisms of action. However, adjuvant therapy has not demonstrated definitive benefit to date and guidelines currently do not support its use. Continued advancement in the understanding of the molecular pathogenesis in RCC is critical, which would lead to identification of new therapeutic targets, as well as novel prognostic and predictive biomarkers, in hopes of improving outcomes in this lethal disease. Herein we summarize the results of randomized studies of the adjuvant treatments of RCC, in hopes to direct future effort in the development of treatment of this disease.

Neoadjuvant chemotherapy and primary debulking surgery utilization for advanced-stage ovarian cancer at a comprehensive cancer center.

OBJECTIVE: The aim of this study was to evaluate the use of neoadjuvant chemotherapy (NACT) and primary debulking surgery (PDS) before and after results from a randomized trial were published and showed non-inferiority between NACT and PDS in the management of advanced-stage ovarian carcinoma. METHODS: We evaluated consecutive patients with advanced-stage ovarian cancer treated at our institution from 1/1/08-5/1/13, which encompassed 32 months before and 32 months after the randomized trial results were published. We included all newly diagnosed patients with high-grade histology and stage III/IV disease. Associations between the use of NACT and clinical variables over time were evaluated. RESULTS: Our study included 586 patients. Median age was 62 years (range, 30-90); 406 patients (69%) had stage III disease, and 570 (97%) had disease of serous histology. Twenty-six percent (154/586) were treated with NACT and 74% (432/586) with PDS. NACT use increased significantly from 22% (56/256) before 2010 (at which point the results of the randomized trial were published) to 30% (98/330) after 2010 (p=0.037). Although patients who underwent PDS were more likely to experience grade 3/4 surgical complications than those who underwent NACT, those selected for PDS had a median OS of 71.7 months (CI, 59.8-not reached) compared with 42.9 months (CI 37.1-56.3) for those selected for NACT. CONCLUSIONS: In this single-institution analysis, the best survival outcomes were observed in patients who were deemed eligible for PDS followed by platinum-based chemotherapy. Selection criteria for NACT require further definition and should take institutional surgical strategy into account.

Recent trends and predictors of multimodality treatment for oesophageal, oesophagogastric junction, and gastric cancer: A Dutch cohort-study.

BACKGROUND: In recent years, evidence supporting multimodality treatment for oesophageal, oesophagogastric junction (OGJ), and gastric cancer has accumulated. This population-based cohort-study investigates trends and predictors of utilisation of multimodality treatment for oesophagogastric cancer in the Netherlands. PATIENTS AND METHODS: Data were obtained from the Netherlands Cancer Registry regarding patients with oesophageal (n = 5450), OGJ (n = 2168) and gastric cancer (n = 6683) without distant metastases who had undergone R0 or R1 surgery diagnosed between 2000 and 2012. Follow-up was completed until February 2014. Preoperative/postoperative chemotherapy and/or radiotherapy combined with surgery were considered multimodality treatment. Logistic regression analysis was performed to analyse the association of age, gender, socioeconomic status, clinical T and N classification, hospital type, comprehensive cancer centre network region, and year of diagnosis, with multimodality treatment receipt. Additional analyses were performed to explore differences in trends of utilisation of multimodality treatment between academic and non-academic hospitals. RESULTS: Multimodality treatment utilisation for oesophageal, OGJ and gastric cancer increased significantly to 90%, 85% and 56% in 2012, respectively. In oesophageal and OGJ cancer patients, preoperative chemoradiotherapy was most frequently administered (85% and 47% in 2012, respectively), and in gastric cancer patients preoperative chemotherapy (47% in 2012). Lower age, higher clinical T and N classification, and diagnosis in more recent years were significantly associated with more frequent multimodality treatment receipt. The adoption of most types of multimodality treatment in academic hospitals preceded non-academic hospitals by a year. CONCLUSION: In the Netherlands, the utilisation of multimodality treatment for oesophagogastric cancer has significantly increased during the past decade, especially in oesophageal and OGJ cancer. Multimodality treatment utilisation was especially dependent on patient and tumour characteristics and year of diagnosis, but multimodality treatment trends seem to be related to the publication of landmark studies, participation in nationally running clinical trials, and hospital type, preceding national guidelines.

Adjuvant selenium supplementation in the form of sodium selenite in postoperative critically ill patients with severe sepsis.

INTRODUCTION: Plasma selenium (Se) concentrations are reduced in critically ill surgical patients, and lower plasma Se concentrations are associated with worse outcomes. We investigated whether adjuvant Se supplementation in the form of sodium selenite could improve outcomes in surgical patients with sepsis. METHODS: In this retrospective study, all adult patients admitted to a 50-bed surgical ICU with severe sepsis between January 2004 and April 2010 were included and analysed according to whether they had received adjuvant Se supplementation, which was given at the discretion of the attending physician. When prescribed, Se was administered in the form of sodium selenite pentahydrate (Na2SeO3∙5H2O), in which 100 µg of Se corresponds to 333 µg of sodium selenite. A bolus of sodium selenite corresponding to 1,000 µg of Se was injected intravenously through a central venous line for 30 minutes, followed by infusion of 1,000 µg/day for 24 hours for 14 days until ICU discharge or death. We performed logistic regression analysis to investigate the impact of adjuvant Se supplementation on hospital mortality. RESULTS: Adjuvant Se was administered to 413 (39.7%) of the 1,047 patients admitted with severe sepsis. Age and sex were similar between patients who received adjuvant Se and those who did not. Compared with patients who did not receive adjuvant Se supplementation, patients who did had higher scores on the Simplified Acute Physiology Score II, a greater prevalence of cancer upon admission to the ICU and were more commonly admitted after abdominal surgery. Compared with patients who did not receive adjuvant Se, patients who did had higher hospital mortality rates (46% versus 39.1%; P = 0.027), and longer median (interquartile range (IQR)) ICU stays (15 days (6 to 24) versus 11 days (4 to 24); P = 0.01) and hospital lengths of stay (33 days (21 to 52) versus 28 days (17 to 46); P = 0.001). In multivariable analysis, adjuvant Se supplementation was not independently associated with favourable outcome (odds ratio = 1.19, 95% confidence interval = 0.86 to 1.65; P = 0.288). CONCLUSIONS: In this retrospective analysis of a large cohort of surgical ICU patients with severe sepsis, adjuvant Se supplementation in the form of sodium selenite had no impact on in-hospital death rates after adjustment for confounders.

Patterns of care for men diagnosed with prostate cancer in Victoria from 2008 to 2011.

OBJECTIVE: To describe patterns of care for men diagnosed with prostate cancer in Victoria, Australia, between 2008 and 2011. DESIGN, SETTING AND PATIENTS: Men who were diagnosed with prostate cancer at 11 public and six private hospitals in Victoria from August 2008 to February 2011, and for whom prostate cancer notifications were received by the Prostate Cancer Registry. MAIN OUTCOME MEASURES: Characteristics of men diagnosed with prostate cancer; details of treatment provided within 12 months of diagnosis, according to National Comprehensive Cancer Network risk categories; and characteristics of men who did not receive active treatment within 12 months of diagnosis. RESULTS: Treatment details were collected for 98.1% of men who were assessed as eligible to participate in the study (2724/2776) and were confirmed by telephone 12 months after diagnosis for 74.4% of them (2027/2724). Most patients (2531/2724 [92.9%]) were diagnosed with clinically localised disease, of whom 1201 (47.5%) were at intermediate risk of disease progression. Within 12 months of diagnosis, 299 of the 736 patients (40.6%) who had been diagnosed as having disease that was at low risk of progression had received no active treatment, and 72 of 594 patients (12.1%) who had been diagnosed as having disease that was at high risk of progression had received no active treatment. Of those diagnosed as having intermediate risk of disease progression, 54.5% (655/1201) had undergone radical prostatectomy. Those who received no active treatment were more likely than those who received active treatment to be older (odds ratio [95% CI], 2.96 [2.01-4.38], 10.94 [6.96-17.21] and 32.76 [15.84-67.89], respectively, for age 65-74 2013s, 75-84 2013s and ≥ 85 2013s, compared with < 55 2013s), to have less advanced disease (odds ratio [95% CI], 0.20 [0.16-0.26], 0.09 [0.06-0.12] and 0.05 [0.02-0.90], respectively, for intermediate, high and very high-risk [locally advanced] or metastatic disease, compared with low-risk disease) and to have had their prostate cancer notified by a private hospital (odds ratio [95% CI], 1.35 [1.10-1.66], compared with public hospital). CONCLUSION: Our data reveal a considerable "stage migration" towards earlier diagnosis of prostate cancer in Victoria and a large increase in the use of radical prostatectomy among men with clinically localised disease.

Major changes in chemotherapy regimens administered to breast cancer patients during 2000-2008 in the Netherlands.

There is little information available on the patterns of chemotherapy regimens administered in daily practice to patients with early stage and metastatic or recurrent breast cancer. To determine the trends in type of chemotherapy regimens used in breast cancer patients, newly diagnosed breast cancer patients in the period 2000-2008 who received chemotherapy were identified from the Eindhoven Cancer Registry (ECR) and linked to the PHARMO RLS, including data on, e.g., in- and outpatient drug use. Chemotherapy regimens were classified based on the received combinations and sequences. Trends in the distribution of adjuvant chemotherapy regimens (for early-stage breast cancer) and palliative chemotherapy regimens (for metastatic or recurrent breast cancer) were determined and stratified by Her2/neu status when possible. In this study, 422 patients diagnosed with early-stage breast cancer received adjuvant chemotherapy. The use of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) decreased from 90% in 2000 to almost none since 2005. Administration of regimens that included anthracyclines increased from 4% in 2000 to 96% in 2005, but decreased to 68% in 2008. The use of trastuzumab- and taxane-containing regimens (with or without anthracyclines) increased from 2005 onwards to 24% and 34%, respectively, in 2008. Among the 82 breast cancer patients who received palliative chemotherapy at diagnosis or after breast cancer recurrence, the use of CMF and anthracyclines (without taxanes) decreased, while the use of taxanes (with or without anthracyclines) increased (26% in 2008). Trastuzumab was used as palliative chemotherapy from 2003 onwards, with 22% of the metastatic breast cancer patients receiving trastuzumab-containing regimens in 2008, and bevacizumab was administered since 2007 with 19% of the patients receiving bevacizumab-containing regimens in 2008. In conclusion, major changes have taken place in the chemotherapeutic treatment of patients with early and recurrent breast cancer. These changes reflect the key findings from large clinical trials, as incorporated in the Dutch guidelines.

[Chemotherapy for early breast cancer: practices in 2010]. / Chimiothérapie des cancers du sein non métastatiques: état des lieux en 2010.

The management of breast cancer has changed at both surgery levels, with the development of sentinel node, and at the medical level with the use of new therapies. Breast cancer is a heterogeneous disease and each patient should be offered an adapted treatment in an effort to reduce the risk of relapse and death, with the minimal toxicities. The micrometastatic disease appears early in the history of the tumor and chemotherapy aims to eradicate it. In this review, we describe the state of practice regarding adjuvant and neoadjuvant chemotherapy for early breast cancer.

Cáncer de mama y ácido zoledrónico / No disponible

Material y método: Se realizó una estrategia de búsquedade cáncer de mama con los siguientes descriptores: ácido zoledrónicoy eventos óseos, ácido zoledrónico y mineralizaciónósea, ácido zoledrónico y efecto antitumoral (estudios preclínicosy clínicos).Resultados: La administración de ácido zoledrónico disminuyóde forma significativa el número de metástasis óseas enmujeres con cáncer de mama avanzado.En mujeres premenopáusicas con cáncer de mama y tratamientohormonal adyuvante en un seguimiento a 5 años, ladensitometría ósea de las mujeres que recibieron tratamientocon hormonoterapia y ácido zoledrónico se mantuvo establedurante los tres primeros años y aumentó a los cinco años.Los resultados preliminares de últimos estudios hablan deun efecto sinérgico del tratamiento neoadyuvante y el ácidozoledrónico y de su probable influencia sobre la recidiva y lasupervivencia libre de enfermedad.Conclusiones: Existe evidencia científica acumulada deltratamiento de tumores óseos y metástasis óseas con ácido zoledrónico.La administración de ácido zoledrónico en el tratamientoadyuvante de hormonoterapia parece aumentar la mineralizaciónósea. El ácido zoledrónico con buenos resultadospreliminares en la quimioterapia neoadyuvante promete serun buen candidato junto al tratamiento estándar de las pacientescon cáncer de mama y es un campo en el que se está investigandoampliamente, en espera de resultados definitivos(AU)

Material and method: We have performed a systematic reviewof breast cancer with the following key words: Boneevents and zoledronic acid, bone-mineral density and zoledronicacid, antitumoral activity and zoledronic acid (preclinicaland clinical trials).Results: Treatment with zoledronic acid decreased the incidenceof bone metastases and micro metastases in the bonemarrow of women with advanced breast cancer. In premenopausalwomen with adjuvant endocrine therapy with concomitantzoledronic acid bone loss of bone-mineral density wasprevented during therapy and it was improved at 5 years.There are preliminary that support a sinergistic effect aboutzoledronic acid and neoadjuvant treatment on recurrence anddisease-free survival.Conclusions: There are evidence from zoledronic acid andthe treatment of bone tumors and bone metastases. The treatmentwith zoledronic acid would improve bone-mineral densityin the adjuvant treatment in women with endocrine-responsivebreast cancer. Zoledronic acid with good preliminary results inthe neoadjuvant chemotherapy would be a promise in thestandard management of these patients. There are promisingdifferent therapeutic clinical models studies in this way(AU)

Updates in Gastrointestinal Oncology - insights from the 2008 44th annual meeting of the American Society of Clinical Oncology.

We have reviewed the pivotal presentations rcelated to colorectal cancer (CRC) and other gastrointestinal malignancies from 2008 annual meeting of the American Society of Clinical Oncology (ASCO). We have discussed the scientific findings and the impact on practice guidelines and ongoing clinical trials. The report on KRAS status in patients with metastatic CRC receiving epidermal growth factor receptor (EGFR) targeted antibody treatment has led to a change in National Comprehensive Cancer Network guideline that recommends only patients with wild-type KRAS tumor should receive this treatment. The results of double biologics (bevacizumab and anti-EGFR antibody) plus chemotherapy as first-line treatment in patients with metastatic CRC has shown a worse outcome than bevacizumab-based regimen. Microsatellite Instability has again been confirmed to be an important predictor in patients with stage II colon cancer receiving adjuvant treatment. Adjuvant gemcitabine therapy for pancreatic cancer was investigated by the CONKO-001 study; this resulted in superior survival as compared with observation and can be regarded as an acceptable option, without the addition of radiotherapy. The addition of bevacizumab to gemcitabine and erlotinib was not supior to gemcitabine and erlotinib for advanced disease. Second-line therapy for advanced pancreatic cancer with 5-fluorouracil and oxaliplatin resulted in a survival benefit. Irinotecan plus cisplatin and paclitaxel plus cisplatin result in similar survival when combined with radiotherapy for esophageal cancer. The novel fluoropyrimidine S1 appears to be active in gastric cancer, as a single agent or as combination therapy. Adjuvant intraperitoneal mitomycin-C may decrease the incidence of peritoneal recurrence of gastric cancer. Sorafenib is an effective agent in Asian patients with hepatocellular carcinoma secondary to hepatitis B; its utility in child's B cirrhosis remains to be proven. Sunitinib is also an active agent in hepatocellular carcinoma, and may represent an alterative to sorafenib for advanced disease. These and other important presentations from the 2008 ASCO annual meeting are discussed in this article.

Substantial increase in the use of adjuvant systemic treatment for early stage breast cancer reflects changes in guidelines in the period 1990-2006 in the southeastern Netherlands.

BACKGROUND: This study evaluated trends in adjuvant systemic treatment among breast cancer patients and analyzed the factors on which treatment choice was based. PATIENTS AND METHODS: Patients diagnosed with early stage breast cancer in 1990-2006 were selected from the registry of the Comprehensive Cancer Centre South (n=8261). The probability of receiving therapy was determined per characteristic for the periods 1990-1997, 1998-2001 and 2002-2006, separately. RESULTS: The use of any adjuvant systemic treatment increased from 37% in 1990-1997 to 51% in 1998-2001 and 53% in 2002-2006 (p for trend < 0.0001). In the period 1990-1997, lymph node status (positive vs. negative: probability ratio (PR=25.8; 95% CI, 16.5-40.4) and age ( 60 vs. 35 years: PR=0.01; 95% CI, 0.00-0.02) were the main determinants of the likelihood of receiving chemotherapy. From 1998 onwards, age remained the most important factor in decreasing the likelihood of receiving chemotherapy. During 1990-1997 the use of hormonal therapy was mainly determined by positive lymph node status (PR=35; 95% CI, 25-49) and age ( 70 vs. 35 years: PR=9.3; 95% CI, 4.4-20), whereas positive hormone receptor status mainly affected hormonal therapy use (PR=17; 95% CI, 10-28) in the period 2002-2006. Marked differences were observed between hospitals in the adoption of adjuvant systemic treatment for node-negative patients. CONCLUSIONS: The impact of patient and tumour characteristics on treatment choice varied over time, reflecting major changes in the Dutch treatment guidelines. Patients older than 70 years received almost no chemotherapy.

Induction therapy in the modern era of combined-modality therapy for locally advanced head and neck cancer.

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.

Systemic monotherapy vs combination therapy for CTCL: rationale and future strategies.

There are few approved therapies for cutaneous T-cell lymphoma (CTCL). The retinoids are the major biologic response modifiers used in CTCL, producing good response rates but few complete responses. For patients with early-stage disease, the oral retinoids can be combined with other therapies, such as psoralen plus ultraviolet A or interferon alpha, to improve response rates. Combined-modality therapy with oral retinoids, combined chemotherapy, electron-beam therapy, and topical mustargen has also proved effective. For the treatment of advanced-stage disease, the targeted therapy denileukin diftitox (Ontak) provides a nonimmunosuppressive alternative to conventional chemotherapy or radiation therapy. Of the conventional chemotherapies that have been tested in CTCL, gemcitabine (Gemzar) has demonstrated good efficacy in producing responses, particularly in patients with tumors. This agent can be used in combination with a maintenance therapy of bexarotene (Targretin) to manage the plaques and patches of mycosis fungoides. Several other targeted therapies are now also in testing, for example, alemtuzumab (CamPath), HuMax-CD4, several histone deacetylase inhibitors, and the transition-state inhibitor forodesine. These drugs, in combination with currently used therapies, may increase the number and combinations of therapies available for the treatment of this chronic condition to optimize long-lasting responses in CTCL.

Adjuvant treatment of colon cancer: past, present and future.

This manuscript summarizes recent progress in the adjuvant treatment of colon cancer. 5-Fluorouracil plus leucovorin, that have been considered standard therapy over the last 15 years, have now been replaced by combination chemotherapy, at least in stage III disease. The treatment of stage II disease is still somewhat less established. Prognostic and predictive biological markers are urgently needed for further fine-tuning of therapy. Molecular targeted agents have been developed with proven activity in advanced disease and are now being assessed in the adjuvant setting. It is expected that the inclusion of these new agents will lead to a further enhancement of treatment outcome. Those involved in the treatment of colorectal cancer should be encouraged to continue to provide optimal patient care and to participate in clinical trials in order to increase the evidence on which they can base their clinical judgement and to make further progress.