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PubMed2004

Prevalence and risk factors for ischemia, leak, and stricture of esophageal anastomosis: gastric pull-up versus colon interposition.

BACKGROUND: Reports of esophageal anastomotic complications often involve more gastric than colonic reconstructions and are incomplete because of fragmented followup by physicians unfamiliar with the surgical procedure. STUDY DESIGN: Three hundred ninety-three consecutive esophagectomy patients had prevalence and risk factors determined for graft ischemia and anastomotic leak; 363 of these patients followed for more than 1 month (median 15 months) had prevalence and risk factors determined for anastomotic stricture. RESULTS: Conduit ischemia occurred in 36 (9.2%) and anastomotic leak in 43 patients (10.9%). Risk factor for ischemia was comorbid conditions requiring therapy (Odds ratio [OR]: 2.2 [95% CI 1.1-4.3]), and for leak were ischemia (OR: 5.5 [95% CI 2.5-12.1]), neoadjuvant therapy (OR: 2.2 [95% CI 1.1-4.5]), and comorbid conditions (OR: 2.1 [95% CI 1.1-3.9]). A stricture developed in 80 patients (22.0%). Risk factors were ischemia (OR: 4.4 [95% CI 2.0-9.6]), anastomotic leak (OR: 3.8 [95% CI 1.9-7.6]), and increasing preoperative weight (p = 0.022). The prevalence of ischemia was similar after gastric (10.4%) versus colonic (7.4%) reconstruction; leak and stricture were more common (14.3% versus 6.1%, p = 0.013, 31.3% versus 8.7%, p < 0.0001, respectively) and strictures were more severe (11.2% versus 2%, p = 0.001) after gastric pull-up. Patients free of ischemia and leak who developed stricture were more likely to have had a gastric pull-up (25% versus 7%, p < 0.0001). Dilatation was effective treatment in 93% of patients. CONCLUSIONS: After esophagectomy 10% of patients will develop conduit ischemia or an anastomotic leak and 22% will develop anastomotic stricture. Anastomotic leak and strictures are more common and the strictures are more severe after gastric pull-up compared with colon interposition. Dilatation is a safe and effective treatment.

Anastomosis, Surgical↗

PubMed2004

Temporal effect of neoadjuvant androgen deprivation therapy on PSA kinetics following permanent prostate brachytherapy with or without supplemental external beam radiation.

PURPOSE: To evaluate the effect of neoadjuvant androgen deprivation therapy on PSA kinetics following brachytherapy with or without supplemental external beam radiation therapy (XRT), to evaluate the magnitude and duration of the peak PSA, and to compare potential differences in PSA response curves between biochemically disease-free and failed patients. MATERIALS AND METHODS: From November 1995 through August 2000, 179 consecutive patients with clinical T1b-T3a NxM0 (2002 AJCC) prostate cancer received neoadjuvant androgen deprivation therapy (median, 4 months) prior to brachytherapy using (103)Pd or (125)I with or without supplemental XRT. The median follow-up was 56 months. Following brachytherapy, PSA determinations were obtained at 3 months and then every 6 months thereafter. A median and mean of 9 and 9.5 PSA determinations, respectively, were obtained per patient. Biochemical disease-free survival was defined by the ASTRO and Houston definitions with both definitions used to determine the rate of overestimation of early biochemical failure secondary to testosterone recovery. RESULTS: Although a trend for higher baseline and peak PSA was noted in (125)I monotherapy patients, the difference between the 4 groups was not statistically significant (p = 0.088). Changes in PSA over time, however, were statistically significant (p = 0.042). For all 4 groups, the peak PSA occurred approximately 15-21 months following brachytherapy. For biochemically disease-free patients, the median PSA increase above nadir was 0.1 ng/mL, and the median number of consecutive rises in PSA was 1. Using the ASTRO and Houston definitions, only 2.3% and 0.6% of patients would have been inadvertently scored as failures. CONCLUSIONS: In brachytherapy patients receiving 3-6 months of neoadjuvant androgen deprivation therapy, the median PSA increase above nadir was 0.1 ng/mL. The ASTRO and Houston definitions of biochemical failure inadvertently scored only 2.3% and 0.6% of patients as failures.

Adenocarcinoma↗

PubMed2004

Inflammatory breast carcinoma: outcomes with trimodality therapy for nonmetastatic disease.

BACKGROUND: The objectives of this study were to summarize a single-institution experience in treating patients with inflammatory breast carcinoma (IBC) using trimodality therapy and to identify prognostic factors for outcome. METHODS: Sixty-one women underwent radiation therapy with curative intent for IBC between 1982 and 2001. All but five women received trimodality therapy. Neoadjuvant chemotherapy was given to the majority of women (n = 43 patients), although some received "up-front" surgery as first therapy (n = 18 patients). RESULTS: With a median potential observation time after diagnosis of 14 years, freedom from locoregional disease progression was 78%, freedom from distant metastasis was 45%, and the cause-specific survival rate was 47% at 5 years. Approximately 40% of the 56 patients who received trimodality therapy remained free of disease. Multivariate analysis demonstrated three factors that were found to be associated significantly with improved cause-specific survival: pathologic tumor size < 4 cm (P = 0.0001), up-front surgery (P = 0.0078), and local disease control (P = 0.0003). Factors that were found to be associated with better freedom from locoregional disease progression were pathologic tumor size (< 4 cm; P = 0.0157), age (> 55 years; P = 0.0596), and radiation dose (> or = 60 grays [Gy]; P = 0.0621). CONCLUSIONS: IBC is an aggressive disease that is treated effectively in select patients by multimodality therapy. Patient outcomes may be improved with therapies that result in better local and systemic control. Further studies are warranted to address the optimal sequence of trimodality therapy and the optimal administration of each agent.

Adult↗

PubMed1997

Liver-directed therapies for gastrointestinal malignancies.

Although surgery remains the treatment of choice for hepatic malignancy, both primary and secondary, the majority of patients presenting with hepatic tumors are unfortunately not candidates for resection. A number of alternative hepatic-directed therapies are assessed for their role in the following settings: as primary treatment modalities; as treatment adjuvants to surgical resection, including neoadjuvant therapy to downstage tumors prior to planned resection; and as a means of palliation when tumors are incurable. Non-surgical hepatic-directed therapies demonstrated to prolong survival include adjuvant portal vein chemotherapy infusion at the time of resection of primary colorectal cancer, and hepatic artery infusion in the setting of established hepatic metastases. Several other therapies are described but remain incompletely evaluated, including transplantation, microwave coagulation, injection of radiolabeled particles, chemoembolization, percutaneous ethanol injection, and cryosurgery. Due to the rarity of these tumors, many studies present results of heterogeneous populations of patients, making meaningful comparison difficult. Finally, it must be said that screening asymptomatic patients after resection of colorectal cancer with a view to application of hepatic-directed therapy in the setting of colorectal metastases is costly.

Carcinoma, Hepatocellular↗

PubMed2000

Surgical salvage therapy: abdominoperineal resection for recurrent anal carcinoma, metastasectomy of recurrent colorectal cancer, and esophagectomy after combined chemoradiation.

This review highlights the advances in the salvage surgical therapies for recurrent disease after definitive therapy of anal carcinoma, colorectal cancer, including liver metastasectomy, and esophageal carcinoma treated primarily with chemoradiation. New diagnostic modalities, advances in neoadjuvant therapies for unresectable liver metastases, and, in addition, the importance of adjuvant hepatic arterial chemotherapy after curative liver resections are reviewed. Although chemoradiation is not the standard of care for esophageal cancer, salvage esophagectomy after such treatment is discussed. Definitive chemoradiation for squamous cell carcinoma of the anus has altered the role of surgical intervention to a salvage option instead of primary treatment. Although this is not yet the case for esophageal carcinoma, recent improved chemoradiation regimens have been reported by the French and Japanese, who use surgery for nonresponders. For recurrent colorectal carcinoma, including liver-only metastases, patients can be rendered disease free after surgical extirpation with evidence of improved survival. Appropriate surveillance in these patients may identify subsets of patients with disease amenable to resection.

Abdomen↗

PubMed2000

Docetaxel: an update of its use in advanced breast cancer.

UNLABELLED: Docetaxel, a semisynthetic member of the taxoid class of antineoplastic agents, is effective in the treatment of patients with advanced (locally advanced or metastatic) breast cancer. Reported objective response rates for docetaxel 100 mg/m2 ranged from 54 to 69% and 53 to 82% as first-line monotherapy or combination therapy, respectively. Objective response rates of 23 to 65% and 30 to 81% have been reported for docetaxel as second-line monotherapy or combination therapy, respectively. In Japanese studies, second-line docetaxel 60 mg/m2 produced objective response rates of 42 to 55%. At the recommended dose of 100 mg/m2 given as a 1-hour intravenous (i.v.) infusion every 3 weeks, docetaxel had significantly greater efficacy than doxorubicin, mitomycin plus vinblastine and methotrexate plus fluorouracil, and similar efficacy to fluorouracil plus vinorelbine in pretreated patients with advanced breast cancer. In chemotherapy-naive patients, first-line combined therapy with docetaxel and doxorubicin had significantly greater efficacy than doxorubicin plus cyclophosphamide. Promising results have been achieved in phase I/II trials of a weekly regimen of docetaxel (generally 30 to 45 mg/m2). Preliminary data indicate a potential role for docetaxel in the neoadjuvant therapy of early breast cancer. The major dose-limiting adverse event associated with docetaxel is neutropenia. Although other adverse events are common, the tolerability profile of docetaxel is generally acceptable in the majority of patients, particularly in comparison with other antineoplastic regimens. CONCLUSIONS: Although no single standard regimen has been identified as optimal for the treatment of advanced breast cancer, phase III trials have shown that docetaxel has improved efficacy over doxorubicin alone (considered one of the current gold standards), methotrexate/fluorouracil and mitomycin/vinblastine in second-line therapy. In combination with doxorubicin, docetaxel has demonstrated better efficacy than doxorubicin/cyclophosphamide in first-line therapy. These results provide a basis for therapy choice in advanced breast cancer. Clinical trials comparing docetaxel monotherapy versus paclitaxel monotherapy and versus docetaxel combination therapy are warranted. The role of docetaxel in the adjuvant and neoadjuvant treatment of early breast cancer is being evaluated.

Antineoplastic Agents, Phytogenic↗

PubMed2003

Gastrointestinal stromal tumours.

BACKGROUND: Gastrointestinal stromal tumours (GISTs), previously classified as benign or malignant smooth muscle tumours, are the most common mesenchymal tumours of the gastrointestinal tract. GISTs express a growth factor receptor with tyrosine kinase activity, termed KIT. Mutations of KIT are common in malignant GISTs and lead to constitutional activation of tyrosine kinase function, which causes cellular proliferation and resistance to apoptosis. GISTs are notoriously unresponsive to chemotherapy and, until the recent introduction of the KIT inhibitor imatinib, there has been no effective therapy for advanced, metastatic disease. METHODS: A Medline literature search was preformed to locate all articles relating to gastrointestinal tumours, GISTs, KIT and imatinib. RESULTS AND CONCLUSIONS: The 5-year survival rate after complete resection of GISTs is approximately 50 per cent. The median duration of survival for patients with a metastatic GIST is approximately 20 months, and 9-12 months for patients with local recurrence. Phase II trials have investigated the effect of imatinib on irresectable or metastatic GISTs. In these trials more than 50 per cent of patients responded to imatinib within a few months and approximately 12 per cent had disease progression. Uptake of [(18)F]fluoro-2-deoxy-D-glucose demonstrated by positron emission tomography has been found to be reduced after starting imatinib. The potential for cure and the optimal length of treatment is currently unknown. Imatinib is the first effective systemic therapy for metastatic and locally irresectable GISTs. Large multi-institutional clinical trials to investigate the efficacy of imatinib as adjuvant or neoadjuvant therapy for GISTs are now required.

Antineoplastic Agents↗

PubMed1997

Role of vindesine as neoadjuvant chemotherapy for non-small cell lung and head and neck cancers.

Although surgery is the only therapeutic intervention with potential for cure of non-small cell lung cancer (NSCLC) and head and neck cancer, most patients present with tumors that are too far advanced for resection. For this reason, neoadjuvant chemotherapy is being increasingly used to down-stage primary tumor burden before surgery. The procedure offers the possibility of enhancing resectability and thereby improves the chances of achieving complete eradication. In NSCLC, the most successful results have been obtained in patients with disease that is localized to the thorax and in those achieving complete responses to chemotherapy. A number of different combination regimens have been studied with cisplatin as the key component. Response rates of up to 88% have been reported together with complete sections in up to 74% of patients. The impact on survival is still to be determined. Although there is ample data showing that combination regimens containing vindesine have a favorable effect on survival in patients with inoperable NSCLC, relatively few of the studies have evaluated these regimens for use as neoadjuvant therapy. New studies should focus on increasing the complete response rate above the 20% level that is currently attainable. The results using neoadjuvant chemotherapy in head and neck cancer are disappointing with no survival benefit demonstrated. However, neoadjuvant chemotherapy may help preserve organ function and thus improve quality of life of patients.

Antineoplastic Agents, Phytogenic↗

PubMed1991

Ifosfamide/mesna. A review of its antineoplastic activity, pharmacokinetic properties and therapeutic efficacy in cancer.

Ifosfamide is an oxazaphosphorine alkylating agent with a broad spectrum of antineoplastic activity. It is a prodrug metabolised in the liver by cytochrome P450 mixed-function oxidase enzymes to isofosforamide mustard, the active alkylating compound. Mesna, a uroprotective thiol agent, is routinely administered concomitantly with ifosfamide, and has almost eliminated ifosfamide-induced haemorrhagic cystitis and has reduced nephron toxicity. Therapeutic studies, mostly noncomparative in nature, have demonstrated the efficacy of ifosfamide/mesna alone, or more commonly as a component of combination regimens, in a variety of cancers. In patients with relapsed or refractory disseminated nonseminomatous testicular cancer, a salvage regimen of ifosfamide/mesna, cisplatin and either etoposide or vinblastine produced complete response in approximately one-quarter of patients. As a component of both induction and salvage chemotherapeutic regimens, ifosfamide/mesna has produced favourable response rates in small cell lung cancer, paediatric solid tumours, non-Hodgkin's and Hodgkin's lymphoma, and ovarian cancer. Induction therapy with ifosfamide/mesna-containing chemotherapeutic regimens has been encouraging in non-small cell lung cancer, adult soft-tissue sarcomas, and as neoadjuvant therapy in advanced cervical cancer. As salvage therapy, ifosfamide/mesna-containing combinations have a palliative role in advanced breast cancer and advanced cervical cancer. Ifosfamide/mesna can elicit responses in patients refractory to numerous other antineoplastic drugs, including cyclophosphamide. With administration of concomitant mesna to protect against ifosfamide-induced urotoxicity, the principal dose-limiting toxicity of ifosfamide is myelosuppression; leucopenia is generally more severe than thrombocytopenia. Reversible CNS adverse effects ranging from mild somnolence and confusion to severe encephalopathy and coma can occur in approximately 10 to 20% of patients after intravenous infusion, and the incidence of neurotoxicity may be increased to 50% after oral administration because of differences in the preferential route of metabolism between the 2 routes of administration. Other adverse effects of ifosfamide include nephrotoxicity, alopecia, and nausea/vomiting. In general, intravenously administered mesna is associated with a low incidence of adverse effects; however, gastrointestinal disturbances are common following oral administration. Thus, ifosfamide/mesna is an important and worthwhile addition to the currently available range of chemotherapeutic agents. It has a broad spectrum of antineoplastic activity and causes less marked myelosuppression than many other cytotoxic agents. At present, the role of ifosfamide/mesna in refractory germ cell testicular cancer is clearly defined; however, its overall place in the treatment of other forms of cancer awaits delineation in future well-controlled comparative studies.

Drug Evaluation↗

PubMed1989

Systemic chemotherapy in the management of bladder cancer.

The treatment of bladder cancer is in a state of evolution. With the advent of effective chemotherapy, multimodal treatment planning is needed to ensure the best results. This requires the participation of the urologist, medical oncologist, radiologist, and radiation therapist in order to determine the optimal treatment strategy for each patient. Currently, radical cystectomy should be considered standard therapy. Neoadjuvant or true adjuvant chemotherapy are still investigational. Randomized trials should be designed to define those patients who will benefit from combined modality therapy, the sequence in which it should proceed, and its impact on disease-free and total survival. Certain principles in patient management require emphasis. 1. The patient must be carefully staged prior to treatment and later restaged thoroughly; whenever possible pathologic confirmation is recommended. Following chemotherapy, all sites of measurable and evaluable disease should be reassessed. Patients with residual masses may have only fibrosis, or microscopic tumor, and complete resection may result in prolonged disease-free survival. 2. Cystectomy after chemotherapy appears to be indicated when this is the only site of disease. If a patient responds systemically with a CR, but has residual disease in the bladder, salvage cystectomy may translate into a prolonged survival. Similarly, a patient who relapses in the bladder following chemotherapy should have surgery. It is unclear if patients with initially unresectable disease who are downstaged (PR) to a resectable lesion should undergo surgery or be consolidated with radiation therapy. 3. Adequate renal function is needed to give optimal doses of chemotherapy. Patients with ureteral obstruction often benefit from a nephrostomy tube. The creatinine clearance may improve following urinary diversion to allow full-dose chemotherapy.

Antineoplastic Agents↗

PubMed2004

Complexity in the treatment of pulmonary large cell neuroendocrine carcinoma.

PURPOSE: According to the World Health Organization (WHO) classification of pulmonary large cell neuroendocrine carcinoma (LCNEC), one of the neuroendocrine tumors of the lung, is considered as a variant of non-small cell lung carcinoma. The objective of this study was to investigate the treatment strategy for LCNEC. METHODS: We retrospectively reviewed the clinical information of 12 patients with LCNEC. RESULTS: Three patients with stage I disease underwent curative resection but all relapsed within 20 months. One with stage IIA disease underwent non-curative resection received adjuvant chemoradiotherapy (cisplatin plus etoposide) and is well with no evidence of recurrence. Two with stage IIIB disease received concurrent chemoradiotherapy. Both achieved partial response (PR) but relapsed within 2 months. One elderly patient with stage IIIA disease received vinorelbine alone and did not respond. Of five patients with stage IV disease, three received platinum-based chemotherapy but no patient achieved PR. Of five patients with gefitinib as salvage therapy, one achieved PR. CONCLUSIONS: The prognosis of LCNEC is poor. To improve the outcome, we must evaluate the effectiveness of adjuvant or neoadjuvant therapy in patients with resectable disease. In addition, the evaluation of systemic and multimodality treatment strategies similar as in small cell lung cancer is worthy of consideration.

Adult↗

PubMed1996

Locally advanced noninflammatory breast cancer.

Treatment of locally advanced noninflammatory breast cancer has changed markedly over the past 50 years. Haagensen's description of the clinical signs that define inoperable and operable tumors was the first realization that radical surgery alone could not cure the majority of women with locally advanced disease. Studies of the use of local therapy alone (surgery or radiation therapy) confirmed that most patients developed both distant metastatic disease and a high rate of local-regional failure. Combination surgery and radiation therapy regimens improved local control but did not influence long-term survival. The advent of successful multimodal regimens incorporating systemic treatment (chemotherapy or chemohormonal therapy) as well as local therapy (surgery and radiation) has significantly improved disease-free and overall survival as well as local-regional control. The benefits of neoadjuvant and adjuvant chemotherapy regimens have been debated. Neoadjuvant therapy allows clinical and pathologic assessment of tumor response to the chemotherapy regimen. In addition, local-regional control seems to be improved, and reductions in the size of the primary tumor allow breast-preserving procedures, even in patients initially not believed to be candidates for resection. Longer follow-up of these conservatively treated patients will be needed, however, to determine whether local-regional control is preserved.

Breast Neoplasms↗

PubMedDate not supplied

En bloc resection for locally advanced cancer of the pancreas: is it worthwhile?

The benefit of radical surgical resection of contiguously involved structures for locally advanced pancreatic cancer is unclear. The aim of this study was to examine patient outcome after extended pancreatic resection for locally advanced tumors and to determine if any subset of extended resection affected outcome. We retrospectively reviewed the records of 116 patients with adenocarcinoma of the pancreas, who underwent extirpative pancreatic surgery between 1987 and 2000. Of the 116 patients, 37 (32%) required resection of surrounding structures (group I), and 79 patients (68%) underwent standard pancreatic resections (group II). In all cases, all macroscopic disease was excised. In group I a total of 46 contiguously involved structures were resected: vascular in 25 patients (54%), mesocolon in 16 (35%) (colic vessels in 3, colon in 13), adrenal in three (7%), liver in one (2%), stomach in one (2%) (for a tumor in the tail of the pancreas), and multiple structures in four. Excision of regional blood vessels included the superior mesenteric vein and/or portal vein in 16, hepatic artery in five, and celiac axis in four. No differences between groups I and II were detected for any of the following parameters: age, sex, history of previous operation, estimated blood loss, or hospital stay. For the entire cohort the morbidity and mortality were 38% and 1.7%, respectively, and these rates were similar in the two groups. Adjuvant therapy was administered to more than 90% of patients in both groups. However, patients in group I were more likely to have received neoadjuvant therapy (76% vs. 42%, P = 0.001). Total pancreatectomy and distal pancreatectomy were more often performed in group I (P = 0.005). Additionally, the median operative time was longer (8.5 hours compared to 6.9 hours (P = 0.0004)). Both groups had similar rates of microscopically positive margins and involved lymph nodes, as well as total number of lymph nodes removed. The median survival was 26 months for patients in group I and 16 months for patients in group II (P = 0.08). The median disease-free survival for groups I and II was 16 months and 14 months, respectively (P = 0.88). In comparing patients in group I, who underwent vascular resection vs. mesocolon (colon or middle colic vessels) resection, the median survival was 26 months and 19 months, respectively (P = 0.12). We were unable to detect a difference in outcome for patients with locally advanced cancers requiring extended pancreatic resections compared to patients with standard resections. En bloc resection of involved surrounding structures, to completely extirpate all macroscopic disease, may be of benefit in selected patients with locally advanced disease, particularly when combined with preoperative chemoradiation therapy.

Adenocarcinoma↗

PubMed2002

Endoscopic Nd:YAG laser with aggressive multimodality therapy for locally advanced esophageal cancer.

BACKGROUND: Laser therapy of esophageal carcinoma has been limited to management of malignant dysphagia. To investigate its cytoreductive potential, Nd:YAG laser tumor debulking was added to multimodality therapy. METHODS: From 1994-1998, 29 patients with advanced locoregional esophageal carcinoma were enrolled in a prospective experimental study of high-dose neoadjuvant chemoradiotherapy together with endoscopic Nd:YAG laser photoablation. Comparisons were made to a retrospective cohort of 31 patients treated from 1990 to 1994 who underwent similar neoadjuvant chemoradiotherapy without laser debulking. RESULTS: Laser dosage ranged from 3457 to 67,443 J (mean 21,832 [SD 16,999]) delivered in 1 to 6 (mean 2.6 [1.4]) treatment sessions. Actuarial analysis showed improved survival in the laser-treated group versus the reference group (30.1 months vs. 16.5 months; p = 0.047). Multivariable analysis of the impact of age, T-stage, N-stage, completion of neoadjuvant therapy, and laser debulking that included all patients in both treatment groups showed completion of therapy to be the most significant variable associated with survival. There were 3 complications related to laser therapy. Relief of dysphagia was achieved in 19 of 29 patients (66%) in the laser group versus 13 of 31 (42%) in the reference group. CONCLUSIONS: Malignant dysphagia may be more effectively treated by the addition of Nd:YAG laser therapy to aggressive multimodality therapy. Improved survival with the addition of laser debulking warrants longer follow-up and a prospective comparative trial.

Adult↗

PubMed1997

[Guidelines for stomach carcinoma and lymphoma].

The manual is based on a consensus-conference of the oncological study groups surgery, internal medicine and radio therapy. Additionally to gastrectomy and exceptionally the high resection it contains lymphdysection of the second compartment. When R0 resection seems impossible preoperatively, a neoadjuvant therapy under study protocol should take place. Especially in gastric lymphoma the therapeutical variety is large. Therefore taking part in clinical studies is urgently required.

Carcinoma↗

PubMed2006

Rising prostate-specific antigen values during neoadjuvant androgen deprivation therapy: The importance of monitoring.

PURPOSE: To assess the impact of a rising prostate-specific antigen (PSA) level in patients receiving neoadjuvant androgen deprivation therapy (N-ADT) before external beam radiotherapy for prostate cancer. METHODS AND MATERIALS: From prospectively collected data, we identified 182 patients who received between 3 and 12 months of N-ADT before definitive external beam radiotherapy and who had at least three PSA readings during the neoadjuvant period. One hundred fifty patients had PSA values that continued to fall (Non-Rise group), but 32 had a PSA value that started to rise (Rise group). The two groups were compared by Mann-Whitney U and Pearson chi-square tests. Kaplan-Meier and log-rank analyses were performed for time to treatment failure, cause-specific survival (CSS), and overall survival (OS). RESULTS: The median follow-up was 62.5 months for the Non-Rise group and 53 months for the Rise group. Patients who sustained a PSA rise during the N-ADT period had a shorter time to PSA relapse (p = 0.013), poorer CSS (p = 0.027), and poorer OS (p = 0.03). Multivariate analysis confirms the significance of a PSA rise during the N-ADT period for CSS (p = 0.035) and OS (p = 0.038). CONCLUSIONS: A subset of patients treated with N-ADT develop a rising PSA profile that likely represents early androgen resistance. They have significantly worse outcome.

Aged↗

PubMed1999

Prostate specific antigen doubling time after radical prostatectomy: effect of neoadjuvant androgen deprivation therapy.

PURPOSE: We determined the predictors of prostate specific antigen (PSA) doubling time in patients with relapse after radical prostatectomy as well as whether PSA doubling time is shorter in those treated versus not treated with neoadjuvant androgen deprivation therapy. MATERIALS AND METHODS: We calculated PSA doubling time in 204 patients with PSA relapse after radical prostatectomy who were or were not treated with neoadjuvant androgen deprivation therapy. Analysis of covariance was used to determine the effect of clinical and pathological parameters on PSA doubling time, and the proportion of variability explained by these parameters. RESULTS: Clinical stage, and combined clinical stage and margin status, clinical stage and androgen deprivation therapy status, androgen deprivation therapy status and time to PSA relapse, and androgen deprivation therapy status and pretreatment PSA were significant predictors of PSA doubling time. Any variable or combination of variables explained up to only 21% of PSA doubling time variability. When stratified by pretreatment PSA, clinical stage and biopsy grade, the difference in doubling times in patients treated with or without neoadjuvant androgen deprivation therapy was significant only for 4.1 to 10 ng./ml. PSA. In this group mean doubling time plus or minus standard deviation in patients receiving neoadjuvant androgen deprivation therapy and those treated only with radical prostatectomy was 7.6+/-1.0 and 15.4+/-2.6 months, respectively. CONCLUSIONS: Our study indicates that it is difficult to predict PSA doubling time in an individual. The small proportion of variability in PSA doubling time explained by the interaction of androgen deprivation therapy status and other variables indicates that these factors are not clinically significant.

Androgen Antagonists↗

PubMed1995

Non-small-cell lung carcinoma. Current and future therapeutic management.

Non-small-cell lung cancer (NSCLC) is one of the most common malignancies in developed countries and accounts for millions of deaths worldwide. The incidence of NSCLC correlates with smoking tobacco and is likely to increase in those countries with increasing per capita consumption of tobacco. NSCLC is particularly associated with morbidity--in the US several published clinical studies involving a variety of intensive surgical, chemotherapeutic and radiotherapeutic interventions have produced only a 10% 5-year survival. New technologies and breakthroughs in treatment notwithstanding, the current emphasis in clinical trials is to refine and optimise available therapies to maximise patient disease-free and overall survival. These accruing multi-institutional clinical trials may offer surgical resection with or without neoadjuvant therapy, multiagent chemotherapy, and/or standard or hyperfractionated radiation therapy. Since most NSCLC patients have inoperable disease, the most active current trial design entails chemoradiotherapy, since previous trials appear to suggest superior results to radiotherapy alone in these patients.

Carcinoma, Non-Small-Cell Lung↗