Biomedical subjects

M Raderer

Publications and source records attributed to M Raderer.

At least 37 records · Page 2Linked to original sources

PubMed2004

Cytotoxic activity of camptothecin and paclitaxel in newly established continuous human medullary thyroid carcinoma cell lines.

At the time of diagnosis, more than one quarter of patients with medullary thyroid carcinoma (MTC) has distant metastases. Only few of these patients can be cured by surgery. Standard chemotherapy is characterized by low response rates and short response time. The establishment of eight human MTC cell lines provides a new basis for in vitro investigation of cytotoxic drugs. Camptothecin (CPT) and paclitaxel, which never have been investigated in the treatment of MTC, were tested for their cytotoxic profile in comparison with the clinically ineffective dacarbazine. Eight MTC cell lines were established from seven patients with MTC. IC(50) values were calculated from dose-response relationships using cell counts and a formazan dye assay (WST-1). IC(50) values were 3.5 +/- 1.2 nmol/liter for CPT and 8.2 +/- 1.9 nmol/liter for paclitaxel. Dacarbazine showed no reduction of cell proliferation at concentrations 10-fold higher than clinically achievable. Given peak plasma concentrations of 65 +/- 20 nmol/liter for CPT and 1 micro mol/liter for paclitaxel, these promising in vitro results provide a basis for the performance of clinical trials in patients with advanced MTC.

Antineoplastic Agents, Alkylating↗

PubMed2004

The role of nuclear medicine in the diagnosis of cancer of unknown origin.

Cancer of unknown origin (CUO) is defined by the absence of any primary tumour in biopsy-proved metastatic cancer. CUO accounts for a 5-10% of all malignancies. These tumors have a specific biology with clinical characteristics of rapid progression and atypical metastases. Diagnostic evaluation is directed at the identification of treatable subset. Accurate diagnostic workup is crucial because both prognosis and survival rates depend mainly on detection of the primary tumor site. Although these patients undergo extensive imaging procedures, nuclear medicine techniques are under-utilized despite their ability of providing molecular information. Positron emission tomography has an emerging role in this clinical challenge along with other nuclear medicine methods including, bone scan, thyroid scintigraphy.

Biomarkers, Tumor↗

PubMed2003

Occurrence of a pulmonary carcinoid following allogeneic stem cell transplantation for chronic myelogenous leukemia: a case report.

Carcinoid tumors are relatively rare neuroendocrine malignancies with an indolent clinical behavior. The majority of cases arise within the gastrointestinal tract, but they may also be encountered in other organs such as the bronchial system. While occurrence of carcinoid tumors has been reported in association with the multiple endocrine neoplasia (MEN) type I syndrome, no clear-cut risk factors have been established for the development of these malignancies. We report the case of a 50-year-old woman who was diagnosed with a pulmonary carcinoid in 2001 after having undergone allogeneic stem cell transplantation for chronic myeloid leukemia (CML) in 1997. This is the first case report of a carcinoid tumor following allogeneic bone marrow transplantation. At the moment, however, an association with CML as well as a causative role of transplantation and intake of immunosuppressants remains speculative. Apart from highlighting the occurrence of a carcinoid in this setting, our case again underscores the importance of nuclear medicine methods, i.e., somatostatin receptor scintigraphy, in staging and follow-up of patients with carcinoid tumors.

Carcinoid Tumor↗

PubMed2003

Irinotecan plus raltitrexed vs raltitrexed alone in patients with gemcitabine-pretreated advanced pancreatic adenocarcinoma.

There is no established second-line treatment for advanced pancreatic cancer after gemcitabine failure. In view of the urgent need for such therapy, and since preclinical and phase I clinical data suggest an encouraging, potentially synergistic activity between raltitrexed and irinotecan, the present randomised phase II study was initiated. A total of 38 patients with metastatic pancreatic adenocarcinoma, who progressed while receiving or within 6 months after discontinuation of palliative first-line chemotherapy with gemcitabine, were enrolled in this study. They were randomised to 3-weekly courses of raltitrexed 3 mg x m(-2) on day 1 (arm A) or irinotecan 200 mg x m(-2) on day 1 plus raltitrexed 3 mg x m(-2) on day 2 (arm B). The primary study end point was objective response, secondary end points included progression-free survival (PFS) and overall survival (OS), as well as clinical benefit response in symptomatic patients (n=28). In the combination arm, the IRC-confirmed objective response rate was 16% (three out of 19 patients had a partial remission; 95% CI, 3-40%), which was clearly superior to that in the comparator/control arm with raltitrexed alone, in which no response was obtained. Therefore, the trial was already stopped at the first stage of accrual. Also, the secondary study end points, median PFS (2.5 vs 4.0 months), OS (4.3 vs 6.5 months), and clinical benefit response (8 vs 29%) were superior in the combination arm. The objective and subjective benefits of raltitrexed+irinotecan were not negated by severe, clinically relevant treatment-related toxicities: gastrointestinal symptoms (42 vs 68%), partial alopecia (0 vs 42%), and cholinergic syndrome (0 vs 21%) were more commonly noted in arm B; however, grade 3 adverse events occurred in only three patients in both treatment groups. Our data indicate that combined raltitrexed+irinotecan seems to be an effective salvage regimen in patients with gemcitabine-pretreated pancreatic cancer. The superior response activity, PFS and OS (when compared to raltitrexed), as well as its tolerability and ease of administration suggest that future trials with this combination are warranted.

Adenocarcinoma↗

PubMed2003

Early cancer of the stomach arising after successful treatment of gastric MALT lymphoma in patients with autoimmune disease.

BACKGROUND: Extranodal marginal zone B-cell lymphoma of the mucosa associated lymphoid tissue (MALT lymphoma) arises in lymphoid tissue acquired through chronic antigenic stimulation as exemplified by Helicobacter pylori. Secondary development of gastric cancer, however, is thought to be a rare event. The detection of a signet ring cell carcinoma during follow-up endoscopy after successful therapy of MALT lymphoma in a patient with Sjögren's syndrome prompted us to analyse the frequency of subsequent gastric cancer in patients with underlying autoimmune disease (AD). METHODS: Patients with early stage MALT lymphoma and an underlying AD were evaluated for the occurrence of a secondary gastric cancer during the course of follow-up. Data analysed included the type of AD, stage of MALT lymphoma, H. pylori status, treatment for MALT lymphoma and response, follow-up, the presence of a secondary cancer, and time to development of cancer. In all patients, histologic samples were reassessed for the extent of gastritis, presence of intestinal metaplasia or focal atrophy at the time of lymphoma diagnosis. RESULTS: A total of eight patients with overt AD at the time of diagnosis of MALT lymphoma were identified. All patients were women aged between 56 and 77 years; 5 had Sjögren's syndrome, 2 had autoimmune thyroiditis (1 along with psoriasis) and 1 suffered from polymyalgia rheumatica. All patients had early stage MALT lymphoma restricted to the mucosa and submucosa at the time of diagnosis, and the presence of H. pylori was found in all cases. Two of these patients achieved complete remission (CR) of the lymphoma following H. pylori eradication, while six were judged unresponsive and underwent chemotherapy, resulting in CR in all cases. One patient died from stroke while being in CR for 2 months following chemotherapy. Two patients (25%) developed early cancer limited to the gastric mucosa while being in CR from lymphoma for 9 and 27 months, respectively, and underwent partial gastrectomy. Final staging of gastric cancer revealed pT1pN0M0 in both cases. Of the remaining 5 cases, 1 patient had a local lymphoma relapse 18 months after CR and was salvaged with radiotherapy. In the remaining 4 patients, no evidence of lymphoma recurrence or a second malignancy has been found so far by regular follow-up every 3 months for a time-span between 52 and 63 months after initial diagnosis. CONCLUSION: Patients with concurrent MALT lymphoma and an underlying autoimmune condition show not only an impaired response to H. pylori eradication but might also be at increased risk for the development of gastric cancer. In view of this, such patients should be followed closely by regular endoscopies after remission of MALT lymphoma.

Adenocarcinoma↗

PubMed2003

Biweekly high-dose gemcitabine alone or in combination with capecitabine in patients with metastatic pancreatic adenocarcinoma: a randomized phase II trial.

BACKGROUND: Gemcitabine is an active antitumor agent in the treatment of advanced pancreatic cancer, and has shown potential synergistic activity with the oral fluoropyrimidine capecitabine in previous phase I/II trials. Based on this background and in order to define the therapeutic potential and tolerance of this combination more precisely, the present randomized multicenter phase II trial was initiated. PATIENTS AND METHODS: We prospectively randomized 83 patients to treatment with biweekly gemcitabine 2,200 mg/m(2) given as a 30 min intravenous infusion on day 1, or the same treatment plus oral capecitabine 2,500 mg/m(2) given from days 1 to 7. In both arms, chemotherapy was administered for a duration of 6 months unless there was prior evidence of progressive disease. The efficacy of the two treatment arms was evaluated according to standard criteria, i.e. objective response, progression-free survival (PFS) and overall survival (OS), as well as by analysis of clinical benefit response. RESULTS: The overall objective response rate among the 42 patients treated with gemcitabine alone was 14% compared with 7/41 (17%) among those treated with the combination arm. Similar to response rates, there was no apparent difference between the two groups in terms of median PFS (4.0 versus 5.1 months) and median OS (8.2 versus 9.5 months) in the gemcitabine and combination arm, respectively. Of 61 patients with tumor-related symptoms, who were considered evaluable for clinical benefit response, 10/30 (33%) and 15/31 (48.4%) experienced significant palliation in the gemcitabine and combination arm, respectively. Chemotherapy was well tolerated in both arms with only four versus six patients experiencing WHO grade 3 symptoms. Apart from the occurrence of hand-foot syndrome in 10 patients, no major increase in incidence and/or degree of adverse reactions was noted in the combination arm. CONCLUSIONS: Results of this trial suggest a fairly good therapeutic index for the combination of biweekly high-dose gemcitabine and capecitabine for the treatment of advanced pancreatic cancer. Despite a somewhat superior clinical benefit response rate, no advantage over single-agent gemcitabine, however, was noted in terms of objective efficacy parameters.

Adenocarcinoma↗

PubMed2003

Treatment of extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) with mitoxantrone, chlorambucil and prednisone (MCP).

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphoma is a relatively common type of lymphoma arising in various tissues throughout the human body. Currently, there is no standard chemotherapy for advanced stage MALT lymphoma. This has prompted us to retrospectively analyse our experience with the MCP regimen (mitoxantrone, chlorambucil and prednisone) in patients with MALT lymphoma. PATIENTS AND METHODS: Patients with histologically verified MALT lymphoma undergoing chemotherapy with MCP were evaluated retrospectively. The MCP regimen consists of mitoxantrone 8 mg/m(2) intravenously on days 1 and 2, chlorambucil 3 x 3 mg/m(2) per os (p.o.) on days 1-5 and prednisone 25 mg/m(2) p.o. on days 1-5. Information analysed included localisation of the lymphoma, clinical stage, pretreatment, number of chemotherapy cycles administered, toxicity, response to treatment, follow-up time, relapse and survival. RESULTS: A total of 15 patients (six females and nine males aged between 34 and 88 years) with histologically ascertained MALT lymphoma undergoing treatment with the MCP regimen were identified from our records. Ten patients had extragastric lymphoma, while five patients suffered from gastric MALT lymphoma. All patients were chemotherapy-naïve, while two had been locally irradiated before application of MCP for recurrent disease. A total of 74 cycles was administered to our patients, with a median number of five cycles per patient. Eight (53%) patients achieved complete remission, six (40%) patients partial response and only one (7%) patient had progressive disease. Subjective tolerance was excellent, and toxicities were mainly haematological, including granulocytopenia World Health Organisation grade 3 and 4 in three patients each. In two patients, this was accompanied by single episodes of uncomplicated herpes simplex infection. At the time of analysis, all patients are still alive. No relapses have occurred after a median follow-up time of 16 (range 12-29) months. CONCLUSIONS: Our data suggest that MCP is an effective and well-tolerated regimen for treatment of patients with MALT lymphoma irrespective of localisation. Judging from our data, MCP also appears to be a feasible regimen in elderly patients.

Administration, Oral↗

PubMed2003

18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) for assessment of enteropathy-type T cell lymphoma.

BACKGROUND AND AIMS: Enteropathy-type T cell lymphoma (ETCL) represents a relatively rare disease, accounting for less than 1% of non-Hodgkin's lymphomas. ETCL is an aggressive lymphoma which may either present de novo or arise in the context of longstanding or untreated coeliac disease (CD). The aim of this study was to evaluate the potential of 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) for imaging of ETCL. Furthermore, we wished to evaluate whether the presence of CD might provide a potential diagnostic obstacle to imaging of lymphoma due to unspecific 18F-FDG uptake and whether accumulation of 18F-FDG within the gut correlates with activity of CD. PATIENTS AND METHODS: We retrospectively analysed patients with ETCL and individuals suffering from CD undergoing 18F-FDG-imaging at our PET unit. Material for histological reassessment by a reference pathologist had to be available for inclusion of patients in the analysis. Whole body 18F-FDG-PET scans were performed 40 minutes following injection of 300-380 MBq of 18F-FDG. Images were reconstructed iteratively. In areas with focally elevated FDG uptake and in case of diffusely elevated intestinal 18F-FDG accumulation, standard uptake values (SUVs) were calculated. RESULTS: During a period of two years, five patients (one male, four female) with a mean age of 56.4 years (range 44-62) with a diagnosis of ETCL underwent 18F-FDG-PET. Four of these patients were imaged before application of cytotoxic treatment while one patient had regular PET scans for follow up. All four patients undergoing pre-therapeutic imaging showed markedly elevated intestinal 18F-FDG uptake, with a maximal SUV of 6.4-8.0 (mean 7.15 (SD 0.82)). The patient imaged following surgery and cytotoxic therapy had no pathologic 18F-FDG uptake which was found to correlate with normal duodenal mucosa, as evidenced by repeated biopsies and conventional imaging methods. During the same time span, 12 patients (five male, seven female) with a mean age of 63.8 years (range 42-82) suffering from CD were imaged. Four of these patients showed no elevated intestinal 18F-FDG uptake while five had minor diffuse intestinal 18F-FDG accumulation with SUVs ranging between 2.2 and 4.6 (mean 3.4 (SD 0.89)). In the remaining three patients with diffuse intestinal 18F-FDG uptake, no SUV could be calculated. SUVs in patients with ETCL were remarkably higher than in patients suffering from CD (p=0.011), irrespective of the activity of CD at the time of imaging. CONCLUSION: In spite of the relatively small number of patients, our results clearly indicate the potential value of 18F-FDG-PET for diagnosing and imaging ETCL. In addition, the data also suggest that 18F-FDG-PET may lead to early diagnosis in individuals developing ETCL in the context of longstanding CD. This is due to the fact that 18F-FDG does not appear to significantly accumulate in the gut of patients with CD, irrespective of disease activity.

Adult↗

PubMed2003

Second-line treatment of advanced gastric cancer with oxaliplatin plus raltitrexed.

BACKGROUND: Treatment with oxaliplatin plus raltitrexed has demonstrated an encouraging therapeutic index in patients with advanced colorectal cancer and malignant pleural mesothelioma. The aim of this multi-institutional study was to determine the antitumor potential of this combination in patients with metastatic gastric cancer failing prior palliative first-line chemotherapy, and to reconfirm its favorable toxicity profile. PATIENTS AND METHODS: 21 patients with metastatic gastric cancer, who progressed while on or within 6 months after discontinuing palliative first-line chemotherapy, participated in this study. They received raltitrexed 3,0 mg/m(2) and oxaliplatin 130 mg/m(2) both given intravenously on day 1 every 3 weeks. RESULTS: One patient achieved a partial response, 6 had stable disease, and 14 patients progressed. Median progression-free and overall survival from the onset of salvage chemotherapy was 2.0 and 4.5 months, respectively. Hematologic adverse reactions, specifically neutropenia and anemia were common, though generally mild to moderate with only 3 patients experiencing grade 3/4 toxicity. The most frequent non-hematologic adverse events included nausea/emesis, asthenia, and transient elevation of liver functional parameters, again with grade 3 symptoms occurring only in a minority of patients. CONCLUSION: Despite reproducibility of a favorable toxicity profile of oxaliplatin + raltitrexed, our data suggest that this combination regimen has no substantial antitumor activity in patients with progressive, chemotherapeutically pretreated metastatic gastric cancer.

Adult↗

PubMed2003

Primary MALT-lymphoma of the liver: multimodality imaging.

MALT lymphoma rarely affects the liver. We present a case of primary MALT lymphoma of the liver, which appeared as multifocal hyperattenuated lesions compared to the fatty liver on unenhanced CT and as moderately hyperintense on T2-weighted and hypointense on T1-weighted MRI. We describe the radiological imaging features and discuss the differential diagnosis.

Female↗

PubMed2002

Complete remission of chronic plaque psoriasis and gastric marginal zone B-cell lymphoma of MALT type after treatment with 2-chlorodeoxyadenosine.

A 58-year-old woman with a 15-year history of chronic plaque psoriasis was diagnosed with gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. Topical treatment and ultraviolet radiation for therapy of psoriasis had been of limited efficacy. The patient received intravenous treatment with 0.12 mg/kg per day of 2-chlorodeoxyadenosine (2-CDA) over 5 days for management of MALT lymphoma, as it was resistant to eradication of Helicobacter pylori. A total of six cycles were administered from June 1999 until November 1999 (cumulative dose 244.8 mg 2-CDA). After 2 months of 2-CDA administration, psoriatic skin lesions improved significantly, and after 3 months, complete remission of skin lesions was observed. Ongoing complete remission of the MALT lymphoma could be achieved after six cycles of 2-CDA administration. After a follow-up period of 34 months, no recurrence of psoriatic lesions has occurred. The patient is at present free of psoriatic plaques and gastric MALT lymphoma. The course of disease in our patient provides evidence for sustained therapeutic efficacy of 2-CDA in chronic plaque psoriasis in the absence of severe side effects except asymptomatic lymphopenia.

Antineoplastic Agents↗

PubMed2002

Effective combination chemotherapy with paclitaxel and cisplatin with or without human granulocyte colony-stimulating factor and/or erythropoietin in patients with advanced gastric cancer.

A phase II trial was performed to determine the antitumour efficacy and tolerance of combined paclitaxel and cisplatin with or without hematopoetic growth factor support in patients with advanced gastric cancer. Forty-five patients with histologically confirmed metastatic gastric cancer were entered in this trial. Treatment consisted of 2-weekly courses of paclitaxel 160 mg per m2 and cisplatin 60 mg per m2 both given on day 1. Depending on absolute neutrophil counts on the days of scheduled chemotherapeutic drug administration (1000-2000 per microl), a 5-day course of human granulocyte colony-stimulating factor 5 microg x kg(-1) per day was given subcutaneously; in addition, if haemoglobin was <12.0 mg dl(-1), erythropoietin 10 000 IU was administered subcutaneously three times per week. The confirmed overall response rate (intent-to-treat) was 44%, including five complete (11%) and 15 partial remissions (33%). Twelve patients had stable disease (27%), 11 (24%) progressed while on chemotherapy, and two patients were not evaluable. The median time to response was 3 months, the median time to progression 7.0 months, and the median survival time was 11.2 months with 12 patients currently alive. Haematologic toxicity was common, though WHO grade 4 neutropenia occurred in only five patients (11%). Apart from total alopecia in 16 patients (36%), severe non-haematologic adverse reactions included grade 3 peripheral neuropathy in six (13%) and anaphylaxis in two patients. In addition, there was one patient each who experienced grade 3 emesis, diarrhea, and infection, respectively. Our data suggest that the combination of paclitaxel and cisplatin with or without G-CSF and/or erythropoietin has promising therapeutic activity in patients with advanced gastric cancer.

Adenocarcinoma↗

PubMed2002

Positron emission tomography with [18F]2-fluoro-D-2-deoxyglucose (FDG-PET) predicts relapse of malignant lymphoma after high-dose therapy with stem cell transplantation.

We have determined the predictive value of [18F]2-fluoro-2-deoxy-glucose (FDG-PET) in patients with Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL) scheduled for high-dose therapy with stem cell transplantation (HDT/SCT). Inclusion criteria were the presence of an FDG-PET scan after chemotherapy (ChT) within 8 weeks prior to HDT/SCT and available follow-up data. Sixteen patients (10 NHL and six HD) were observed during a follow-up period of 4 to 28 months (median 13 months). Before SCT, five patients had a negative PET, three were weakly positive, two moderately positive, and six strongly positive. None of the five patients with a negative PET before HDT/SCT relapsed and two of three patients with a weakly positive scan are still in remission after HDT/SCT. Of eight patients with a moderate or high positive PET before HDT/SCT, seven relapsed and one died of early HDT/SCT related complications (P< 0.01). Three of eight relapsing patients died of lymphoma 5 to 10 months after SCT and in one additional patient not responding to HDT/SCT, the main cause of death was chronic toxicity 4 months after transplantation. After 12 months, in PET-negative patients the overall and relapse-free survival was 100%, in PET-positive patients 55% and 18%, respectively. In NHL, two patients with negative PET, but with an age-adjusted international prognostic index (AaIPI) of 2 and one with AaIPI = 1 are still in remission. In the seven PET-positive subjects, one patient with AaIPI = 0, three with AaIPI = 1, and two with AaIPI = 2 relapsed. We conclude that FDG-PET is accurate in the prediction of relapse prior to HDT/SCT in patients with lymphoma. It provides additional information when compared with the AaIPI.

Adult↗

PubMed2002

Absence of therapeutic efficacy of the somatostatin analogue lanreotide in advanced primary hepatic cholangiocellular cancer and adenocarcinoma of the gallbladder despite in vivo somatostatin-receptor expression.

BACKGROUND: Carcinoma of the biliary system is a rare tumour entity, and patients with advanced disease face a dismal prognosis. Because of the absence of standard chemotherapy for advanced biliary carcinoma and reports of expression of receptors for somatostatin (SST), we performed a phase II study to evaluate the clinical potential of the long-acting SST analogue lanreotide (LAN) for treatment of this disease. METHODS: Twenty consecutive patients with histologically verified primary hepatic cholangiocellular cancer or primary adenocarcinoma of the gallbladder were enrolled in the study. Before initiation of therapy, SST-receptor scintigraphy using 111In-DOTA-LAN was carried out in eight patients to check for in vivo expression of SST receptors. Thirty milligrams of a slow-release formulation of LAN was administered by deep intramuscular injection every 2 weeks until progression or patients wished to withdraw. Restaging by means of computed tomography was performed every 8 weeks, and response was assessed according to World Health Organisation standard criteria. In addition, weight, performance status, analgesic intake and subjective pain perception were recorded every 4 weeks, along with evaluation of tumour markers CEA and Ca 19-9. RESULTS: Tumour sites were visualized by means of 111In-DOTA-LAN in all 8 patients. A total of 161 injections were administered, the median number per patient being 5 (range 2-36). Side effects were generally mild, only two patients complained of mild nausea and one patient had meteorism attributed to therapy. Therapeutic results, however, were disappointing, with only one patient demonstrating complete remission (CR), which lasted for 18 months before diagnosis of recurrence. Four patients had stable disease (SD) lasting between 3.5 and 9+ months accompanied by weight gain and improvement in performance status in 2 cases, while the remaining 15 patients progressed during therapy. The median time to progression was 2.5 months (range 1-18), and the median survival was 4.5 months (range 1.5-18+ months). No clear-cut correlation between scan result and therapeutic outcome could be demonstrated, as not only the patient with CR and two with SD, but also five patients with progressive disease had a positive scan result. CONCLUSION: Our data show that adenocarcinomas of the gallbladder and hepatic cholangiocellular carcinomas express SST receptors in vivo as judged by 111In-DOTA-LAN scintigraphy. Despite this fact, LAN did not display therapeutic activity in this study.

Aged↗

PubMed2002

Intermittent weekly high-dose capecitabine in combination with oxaliplatin: a phase I/II study in first-line treatment of patients with advanced colorectal cancer.

BACKGROUND: The aim of this phase I study was to determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of an intermittent weekly capecitabine regimen in combination with oxaliplatin. Furthermore, we intended to explore its safety at the recommended dose, and to assess its principal antitumor activity in patients with advanced colorectal cancer. PATIENTS AND METHODS: Thirty patients with measurable metastatic colorectal cancer who previously were unexposed to palliative chemotherapy were enrolled on to this disease-oriented phase I trial. They were treated with a fixed dose of oxaliplatin (85 mg/m(2) administered as a 2-h intravenous infusion on day 1) plus escalating doses of capecitabine (given at two divided daily doses from days 1 to 7), repeated every 2 weeks. The dose of oral fluoropyrimidine was escalated in consecutive cohorts of three to six patients from 2500 to 4000 mg/m(2)/day. After having defined the toxic dose, nine additional patients were entered at the MTD/recommended dose to confirm its safety profile, and assure suitability for future phase II/III studies. RESULTS: In the phase I part of the study, 21 patients were enrolled, and a total of 222 courses were administered through four dose levels of capecitabine combined with oxaliplatin 85 mg/m(2). Gastrointestinal toxicities, predominantly diarrhea, were the principal DLTs. Other severe adverse events included grade 3 asthenia, acute neurological symptoms and skin toxicity. The combination was not myelosuppressive, eliciting only sporadically grade 3/4 neutropenia and/or thrombocytopenia. There was no alopecia, and only a few patients experienced mild symptoms of hand-foot syndrome. Externally reviewed objective responses were noted in 15 of all 30 evaluable patients (overall response rate, 50%; 95% confidence interval 31% to 69%) including three complete remissions and median progression-free survival was 8.8 months (range 7-14+ months). CONCLUSIONS: Overall results of this study indicate that the administration of clinically relevant single-agent doses of both capecitabine and oxaliplatin is feasible and seems to result in promising therapeutic activity in patients with advanced colorectal cancer. On the basis of the toxicological profile of the combination regimen shown in the present study, oxaliplatin 85 mg/m(2) as a 2-h intravenous infusion every 2 weeks administered in combination with capecitabine 3500 mg/m(2)/day x7 in two divided doses is recommended for further evaluations.

Administration, Oral↗

PubMed2002

The impact of hemoglobin levels on fatigue and quality of life in cancer patients.

BACKGROUND: Although fatigue is a commonly reported symptom in cancer patients its etiology is still poorly understood. The objective of the present study was to investigate the relationship between hemoglobin (Hb) levels and the subjective experience of fatigue and quality of life in cancer patients with mild or no anemia undergoing chemotherapy. PATIENTS AND METHODS: Sixty-eight cancer patients (25 colorectal, 26 lung and 17 ovarian cancer) presently undergoing chemotherapy participated in the study. Fatigue was measured with the Multidimesional Fatigue Inventory (MFI-20), quality of life with The European Organization for Research and Treatment of Cancer QLQ-C30. In order to provide normative data for fatigue levels, the MFI-20 was also completed by a sex- and age-matched sample of 120 healthy controls. RESULTS: Compared with healthy subjects, cancer patients experienced significantly higher levels of subjective fatigue. Correlations between Hb values and subscales of the MFI-20 were moderate with a tendency to increase during chemotherapy. Hb values alone, however, do not fully account for the observed fatigue. Other symptoms, especially pain, dyspnea and sleep disturbances, also showed an association with perceived fatigue. CONCLUSIONS: Despite significant correlations, these results indicate that Hb values only partially explain subjectively experienced fatigue and quality of life in cancer patients. It is suggested therefore that the treatment of fatigue must be multidimensional and involve all areas which contribute to the syndrome.

Adult↗

PubMed2002

The clinical role of somatostatin analogues as antineoplastic agents: much ado about nothing?

BACKGROUND: Somatostatin (SST) analogues represent a novel approach for the treatment of certain cancers. The objective of this article is to summarise the current knowledge on SST analogues in the treatment of cancer patients. METHODS: Computerised (Medline) and manual searches were performed to identify publications on clinical trials published in the English-speaking literature between 1966 and 2000. Information abstracted included patients' pre-treatment status, histology, SST receptor (SSTR) evaluation, type of SST analogue, application schedule and dose, duration of treatment, side-effects, response criteria applied (i.e. WHO response criteria, biochemical criteria or symptomatic investigations) and survival. RESULTS: Our search disclosed 22 case reports, five phase 1 and 47 phase II trials, and eight randomised clinical trials using SST analogues (octreotide, lanreotide and vapreotide) as antineoplastic agents. With regard to the phase II trials, conflicting results have been demonstrated in almost all tumour entities investigated. The few randomised studies published so far have shown an impact on survival in patients with hepatocellular cancer, while the effect attributed to treatment in patients with gastrointestinal adenocarcinomas might well have been due to an exceptionally short survival in the control group. There appears to be evidence that SST analogues are able to enhance the therapeutic effects of hormonal intervention in patients with breast cancer, prostate cancer and probably pancreatic cancer. Interpretation of the findings, however, is complicated by the fact that patients were heavily pre-treated in some studies and response criteria have not been uniformly applied. In addition, most studies have not been designed to distinguish between receptor-mediated (direct) and indirect effects of SST analogues in tumour patients. CONCLUSIONS: According to the results obtained so far, there can be no doubt about the wide therapeutic index and the high efficacy of SST analogues in the symptomatic management of neuroendocrine tumours. Apart from these indications, the data do not justify recommendation of SST analogues as antineoplastic agents outside of clinical trials, as the optimal dose and schedule of application for antineoplastic activity has not been defined for currently used agents. Carefully designed clinical trials including investigation of SSTR status before treatment, evaluation of an indirect mechanism of SST analogues, and assessment of optimal combination of hormone therapy and chemotherapy with SST analogues are clearly needed in the near future.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Chemotherapy for management of localised high-grade gastric B-cell lymphoma: how much is necessary?

BACKGROUND: Recent data suggest that chemotherapy with the cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen is a highly effective treatment for localised primary gastric lymphoma of diffuse large B-cell histology (DLBCL). We have reported that the large majority of patients achieve complete remission (CR) following three cycles of treatment, and now provide an updated series with special emphasis on patients receiving only short-term chemotherapy. PATIENTS AND METHODS: All patients with a histologically verified diagnosis of gastric DLBCL in stages EI and EII(1) undergoing chemotherapy with the CHOP regimen were evaluated. Data analysed included clinical stage, histology [presence of an additional mucosa-associated lymphoid tissue (MALT) component], evidence of Helicobacter pylori infection, H. pylori eradication, time to CR, survival and regular restaging (i.e. after three and six cycles, respectively). RESULTS: A total of 37 patients with DLBCL of the stomach with localised disease were identified, five of whom also had a MALT component. Twenty-two patients presented with stage EI and 15 with stage EII(1) disease. All patients were given chemotherapy as sole management of their lymphoma; 36 patients received CHOP, while one patient was given CHOP along with rituximab. Thirty-two (86%) achieved a CR after a maximum of three cycles, while only four patients had to be given six cycles for CR. In total, nine of 37 patients (24%) discontinued therapy earlier than scheduled: one patient received one cycle, two received two, six received three and one patient received four cycles. Two of these patients stopped treatment due to toxicity, i.e. protracted thrombocytopenia or chemotherapy extravasation. One additional patient died after one cycle of treatment; autopsy disclosed no signs of remaining lymphoma. Three patients have died after a median follow-up of 39 months (including the one patient who discontinued therapy after one cycle of treatment), while the remaining 34 patients are alive without evidence of disease. Twenty-four out of 37 patients (65%) had also undergone H. pylori eradication (including six of nine patients receiving only short-term treatment). CONCLUSIONS: DLBCL of the stomach appears to be a highly chemosensitive disease. Our data question the need for full-term CHOP treatment in patients achieving CR upon first follow-up. However, recent data suggest that additional H. pylori eradication might have contributed to the excellent results achieved in our series.

Adult↗