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Volker Heinemann

Publications and source records attributed to Volker Heinemann.

At least 19 recordsLinked to original sources
PubMed2026

Association of ctDNA RAS mutational status and clinical benefits in first-line metastatic colorectal cancer therapy with chemotherapy plus anti-EGFR (overall response rate and progression-free survival): a brief report of systematic review and meta-analysis.

Monitoring RAS mutations in circulating tumor DNA (ctDNA) is increasingly relevant in metastatic colorectal cancer (mCRC). In patients with tissue RAS wild-type (WT) tumors treated with first-line chemotherapy plus anti-epidermal growth factor receptor therapy (1LChT + anti-EGFR), some studies suggest that RAS WT ctDNA is associated with better outcomes, whereas others reported no differences according to ctDNA RAS mutational status. These inconsistencies may be related to small sample sizes, methodological heterogeneity, differences in assay sensitivity and tumor heterogeneity. We performed a systematic review in patients with tissue RAS WT treated with 1LChT + anti-EGFR. PubMed, Web of Science, and Scopus were searched up to April 2026. Risk of bias was assessed using the QUIPS tool, and random-effect models were applied. Fourteen studies met the inclusion criteria (ten non-interventional studies and four clinical trials). Compared with ctDNA RAS mutated tumors, ctDNA RAS WT tumors showed significantly higher overall response rates [ORR: pooled odds ratio (OR) 2.1, 95% confidence interval (CI): 1.3-3.4; P=0.002] and longer progression-free survival [PFS: pooled hazard ratio (HR) 1.6, 95% CI: 1.3-1.9; P<0.001] [non-interventional studies (NIS) + clinical trials (CT) data]. The pooled prevalence of ctDNA RAS mutations was 10.5% (95% CI: 6.2-14.8%). These findings support ctDNA RAS status as a potential biomarker of benefit from anti-EGFR-based therapy in mCRC, although methodological standardization and prospective validation remain necessary.

Circulating tumor DNA (ctDNA)↗
PubMed2007

Importance of performance status for treatment outcome in advanced pancreatic cancer.

Despite progress in the treatment of advanced and metastatic pancreatic cancer (PC), the outcome of this disease remains dismal for the majority of patients. Given the moderate efficacy of treatment, prognostic factors may help to guide treatment decisions. Several trials identified baseline performance status as an important prognostic factor for survival. Unfit patients with a Karnofsky performance status (KPS) below 70% only have a marginal benefit from chemotherapy with gemcitabine (Gem) and may often benefit more from optimal supportive care. Once, however, the decision is taken to apply chemotherapy, KPS may be used to select either mono- or combination chemotherapy. Patients with a good performance status (KPS = 90%-100%) may have a significant and clinically relevant survival benefit from combination chemotherapy. By contrast, patients with a poor performance status (KPS < or = 80%) have no advantage from intensified therapy and should rather receive single-agent treatment.

Clinical Trials as Topic↗
PubMed2007

Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood-brain barrier.

Patients receiving trastuzumab for HER2-overexpressing metastatic breast cancer seem to suffer from an increased risk of brain metastases, even in cases with responsive disease. To evaluate whether trastuzumab is able to penetrate the blood-brain barrier, we measured trastuzumab levels in the serum and in cerebrospinal fluid of metastatic breast cancer patients with brain metastases receiving trastuzumab for HER2-overexpressing metastatic breast cancer. In a pilot study, metastatic breast cancer patients with brain metastases and HER2-overexpressing tumors (HercepTest; Dako, Copenhagen, Denmark) were included. At different time points, trastuzumab levels in the serum and cerebrospinal fluid were measured using a newly developed immunoenzymatic test for trastuzumab. Six out of eight patients were evaluable for determination of trastuzumab level in the serum and cerebrospinal fluid. Before radiotherapy, median trastuzumab level in the serum was 52 054 ng/ml compared with 124 ng/ml in cerebrospinal fluid (ratio 420 : 1). After completion of radiotherapy, median trastuzumab level was 20 185 ng/ml in the serum and 226 ng/ml in cerebrospinal fluid, respectively (ratio 76 : 1). With concomitant meningeal carcinomatosis, trastuzumab level in the serum after radiotherapy was 17 431 and 356 ng/ml in cerebrospinal fluid (ratio 49 : 1). For the first time, we present clinical evidence that trastuzumab levels in cerebrospinal fluid are increased under conditions of an impaired blood-brain barrier such as meningeal carcinomatosis or radiotherapy. This evidence supports the concept of continuing trastuzumab therapy in patients with brain metastases treated by radiotherapy. Monitoring of trastuzumab levels in the serum and cerebrospinal fluid may enable individualized therapy strategies in metastatic breast cancer patients with brain metastases, and lead to a better understanding of trastuzumab pharmacokinetics in the cerebrospinal fluid and serum.

Adult↗
PubMed2006

Randomized phase III trial of gemcitabine plus cisplatin compared with gemcitabine alone in advanced pancreatic cancer.

PURPOSE: To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer. PATIENTS AND METHODS: Patients with advanced adenocarcinoma of the pancreas were randomly assigned to receive either gemcitabine 1,000 mg/m2 and cisplatin 50 mg/m2 given on days 1 and 15 of a 4-week cycle (GemCis arm) or gemcitabine alone at a dose of 1,000 mg/m2 on days 1, 8, and 15 of a 4-week regimen (Gem arm). The primary end point was overall survival; secondary end points were progression-free survival, response rate, safety, and quality of life. RESULTS: One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms. Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival (5.3 months v 3.1 months; hazard ratio [HR] = 0.75; P = .053). Also, median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm (7.5 v 6.0 months), an advantage which did not, however, reach statistical significance (HR = 0.80; P = .15). Tumor response rates were comparable between treatment arms (10.2% v 8.2%). The rate of stable disease was, however, greater in the combination arm (60.2% v 40.2%; P < .001). Grade 3 to 4 hematologic toxicity did not exceed 15% in both treatment arms. CONCLUSION: These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin. Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone, although the difference did not attain statistical significance.

Adult↗
PubMed2006

Prognostic and therapeutic significance of carbohydrate antigen 19-9 as tumor marker in patients with pancreatic cancer.

In pancreatic cancer (PC) accurate determination of treatment response by imaging often remains difficult. Various efforts have been undertaken to investigate new factors which may serve as more appropriate surrogate parameters of treatment efficacy. This review focuses on the role of carbohydrate antigen 19-9 (CA 19-9) as a prognostic tumor marker in PC and summarizes its contribution to monitoring treatment efficacy. We undertook a Medline/PubMed literature search to identify relevant trials that had analyzed the prognostic impact of CA 19-9 in patients treated with surgery, chemoradiotherapy and chemotherapy for PC. Additionally, relevant abstract publications from scientific meetings were included. In advanced PC, pretreatment CA 19-9 levels have a prognostic impact regarding overall survival. Also a CA 19-9 decline under chemotherapy can provide prognostic information for median survival. A 20% reduction of CA 19-9 baseline levels within the first 8 weeks of chemotherapy appears to be sufficient to define a prognostic relevant subgroup of patients ('CA 19-9 responder'). It still remains to be defined whether the CA 19-9 response is a more reliable method for evaluating treatment efficacy compared to conventional imaging.

Adenocarcinoma↗
PubMed2006

Chemoradiotherapy with gemcitabine and continuous 5-FU in patients with primary inoperable pancreatic cancer.

CONTEXT: Gemcitabine and 5-fluorouracil (5-FU) sensitize tumor cells to radiation. Furthermore, 5-FU enhances the cytotoxic effect of gemcitabine. OBJECTIVE: We report the efficacy and the toxicity of concurrent chemoradiation with gemcitabine and 5-FU in the treatment of patients with locally advanced, unresectable pancreatic cancer. PATIENTS: Thirty-two patients (20 men, 12 women; median age 69.9 years) with histologically proven advanced pancreatic carcinoma were included in the study. INTERVENTIONS: The patients received chemotherapy with gemcitabine 300 mg/m2 on days 1, 15, 29 and 5-FU as continuous infusion 350 mg/m2/day of radiation while concurrent radiation (45-50 Gy) was given to the tumor and regional lymph nodes (1.8-2.0 Gy/fraction on 5 days/week). Subsequent to chemoradiotherapy, the treatment was continued with an additional two cycles of gemcitabine (1,000 mg/m2) and cisplatin (50 mg/m2) applied on days 1 and 15 of a four-week cycle. MAIN OUTCOME MEASURES: Patient survival, time to progression, and toxicity of chemoradiation. Tumor responses (complete resolution; partial response; stable disease, and progressive disease) were also evaluated. RESULTS: After the completion of chemoradiotherapy, 2 patients (6.3%) achieved complete resolution and 18 patients (56.3%) a partial response, for an overall response rate of 62.5%. Twelve patients (37.5%) were considered resectable and 9 underwent laparotomy, 7 of whom had definitive pancreatic resection. Four patients had negative surgical margins. With a median follow-up of 49.7 months (95% CI: 48.6-60.8 months) after the completion of chemoradiation, distant metastasis occurred in 25 patients (78.1%) while local recurrence was seen only in 4 of 32 patients (12.5%). Median time to progression was 9.2 months (95% CI: 8.2-10.2 months). Median survival amounted to 13.6 months (95% CI: 12.7-14.6 months) for all patients while it was prolonged to 16.4 months (95% CI: 13.4-19.4 months) for those undergoing secondary resection. In addition, performance status proved to be another prognostic factor for overall survival. The main toxicity of chemoradiation included grade 3-4 leukopenia in 18 patients (56.3%) and thrombocytopenia in 8 patients (25.0%). Episodes of cholangitis were observed in 7 patients (21.9%). CONCLUSION: Gemcitabine and 5-FU can safely be combined with external beam radiation. This preoperative treatment approach is highly effective and appears to improve survival in patients with good performance status and in those who are eligible for a secondary resection.

Aged↗
PubMed2006

Combined chemoradiotherapy for isolated local recurrence after primary resection of pancreatic cancer.

CONTEXT: Primary resectability is expected in up to 20% of pancreatic cancer patients. While most patients relapse with distant metastases, approximately 30% of patients show isolated local recurrence without evidence of distant metastases. OBJECTIVE: The present analysis investigates the efficacy of chemoradiotherapy in this particular patient group. DESIGN: Retrospective study. PATIENTS: Eighteen consecutive pancreatic cancer patients presenting with isolated locoregional recurrence after surgical resection. The median interval between primary surgery and diagnosis of local recurrence was 10.4 months (range: 2.0-19.3 months). INTERVENTIONS: Patients received 3-D conformal radiation with 45 Gy in 25 fractions of 1.8 Gy/day. Simultaneous chemotherapy was employed either with continuous 5-FU infusion, partly in combination with gemcitabine, or with gemcitabine and cisplatin. Sequential chemotherapy with gemcitabine and cisplatin was given to some patients before and after the chemoradiotherapy. RESULTS: In 17 of the 18 patients included, radiotherapy was employed at the intended dose. While WHO grade 3-4 gastrointestinal toxicity was not reported, hematotoxicity was more pronounced. Grades 3 and 4 leukocytopenia occurred in 4 patients (22.2%) and 1 (5.6%) patient, respectively, and grades 3 and 4 thrombocytopenia occurred in 4 patients (22.2%) and 1 patient(5.6%), respectively. Six (37.5%) complete remissions, 6 (37.5%) partial remissions, and 4 (25.0%) stable diseases were noted in 16 evaluable patients. Median progression-free survival calculated from the start of the chemoradiotherapy was 14.7 months (range: 8.4-21.0 months) . Seven (28.9%) patients had another local relapse, while 11 (61.1%) patients developed distant metastases. Median overall survival from the start of the chemoradiotherapy was 17.5 months (95% CI: 15.6-19.4 months) and median survival from the initial diagnosis was 27.2 months (95% CI: 23.9-30.6 months). CONCLUSION: The data provide a first indication that chemoradiotherapy is feasible and may be an effective treatment option in those patients who present with local metastasis after primary surgery for pancreatic cancer.

Aged↗
PubMed2006

RP101 improves the efficacy of chemotherapy in pancreas carcinoma cell lines and pancreatic cancer patients.

RP101 [(E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU)], which supports apoptosis and prevents the acquisition of chemoresistance, was tested in cultured human pancreatic tumor cells. RP101 downregulated uridine phosphorylase, a marker of poor prognosis, and APEX1, which is involved in DNA repair, and repressed Stat3 and its target vascular endothelial growth factor. Furthermore, RP101 activated antitumor immunity as demonstrated by enhanced cytolytic activity of NK-92 natural killer cells. This was concomitant with an enhanced expression of lymphotoxins alpha and beta, natural killer cell transcript 4, tumor necrosis factor LIGHT/TNFSF-14, and intercellular adhesion molecule-1 in pancreas carcinoma cells. These results encouraged us to investigate the effect of RP101 in pancreas cancer patients. Here, we present data from two RP101 combination therapy schemes. In a first pilot study, 13 patients in stage III and VI of the disease were treated with gemcitabine +cisplatin+RP101. RP101 co-treatment enhanced remissions, survival and time to progression. Seventy-seven percent of the patients lived or have lived longer than 1 year, and 23% have lived more than 2 years. Median survival was 447 days, time to progression 280 days and the response rate 33%. A second study with 21 patients in similar stages of disease, treated with RP101+gemcitabine alone, confirmed the results of the pilot study. Eighty-three percent of the presently evaluable patients live or lived 0.5 years or longer and 33% 1 year or longer. Considering both studies, the tumor control was 94%. The data indicate that acquisition of chemoresistance was prevented and the antitumor efficacy of standard chemotherapy was improved. To our knowledge, RP101 co-treatment is more efficient than any other regimen published.

Adult↗
PubMed2005

Chemoradiation for ductal pancreatic carcinoma: principles of combining chemotherapy with radiation, definition of target volume and radiation dose.

Review of the role of chemoradiotherapy in the treatment of locally advanced pancreatic cancer with a specific focus on the technical feasibility and the integration of chemoradiotherapy into multimodal treatment concepts. Combined chemoradiotherapy of pancreatic cancer is a safe treatment with an acceptable profile of side effects when applied with modern planning and radiation techniques as well as considering tissue tolerance. Conventionally fractionated radiation regimens with total doses of 45-50 Gy and small-volume boost radiation with 5.4 Gy have found the greatest acceptance. Locoregional lymphatic drainage should be included in the planning of target volumes because the risk of tumor involvement and local or loco-regional recurrence is high. Up to now, 5-fluorouracil has been considered the "standard" agent for concurrent chemoradiotherapy. The role of gemcitabine given concurrently with radiation has not yet been defined, since high local efficacy may also be accompanied by enhanced toxicities. In addition, no dose or administration form has been determined to be "standard" up to now. The focus of presently ongoing research is to define an effective and feasible regimen of concurrent chemoradiotherapy. While preliminary results indicate promising results using gemcitabine-based chemoradiotherapy, reliable data derived from mature phase III trials are greatly needed. Intensity-modulated radiotherapy has been developed to improve target-specific radiation and to reduce organ toxicity. Its clinical relevance still needs to be defined.

Antimetabolites, Antineoplastic↗
PubMed2005

Re-evaluation of HER2 status in metastatic breast cancer and tumor-marker guided therapy with vinorelbine and trastuzumab.

BACKGROUND: HER2 is overexpressed in 20-30% of breast cancers. Compared to chemotherapy alone, chemotherapy with trastuzumab improves clinical outcome in patients with HER2-positive metastatic breast cancer (MBC). In general, HER2 status in a primary lesion predicts the status of metastases, so that biopsy of metastatic lesions appears unnecessary. CASE REPORT: A 39-year old woman was diagnosed with primary breast cancer in November 2000. Using the method and scoring system of the DAKO Hercep Test, the tumor has shown low HER2 expression (DAKO score 1+). After failure of several chemotherapy regimens for metastatic disease (liver, skeletal), the patient underwent CT-guided needle biopsy of the liver which showed HER2 positive adenocarcinoma (DAKO score 3+). In consequence, the patient was treated with vinorelbine (30 mg/m2 d1,8,15 q4w) and trastuzumab (4 mg/kg loading dose, 2 mg/kg weekly). During a treatment period of 4 months imaging results as well as tumor marker kinetics indicated an excellent response with sustained decrease of tumor markers. A retrospective analysis of the HER2 shed antigen in metastatic stage revealed excessively increased serum levels and supports HER2 overexpression observed in liver metastasis. The kinetics of the HER2 shed antigen during therapy for metastatic disease were found to be in phase with the kinetics of CEA and CA15-3. CONCLUSION: This case report demonstrates that re-evaluation of the HER2 status may be helpful in single patients not sufficiently responding to treatment of metastatic disease. Determination of HER2 overexpression may be facilitated by a determination of the HER2 shed antigen level in peripheral blood.

Adenocarcinoma↗
PubMed2005

How harmful is contralateral testicular biopsy?--an analysis of serial imaging studies and a prospective evaluation of surgical complications.

OBJECTIVE: Testicular biopsy has recently gained a role in early detection of testicular cancer. However, its use is still limited mainly because of the fear of untoward consequences. There is a paucity of data regarding unfavourable effects of testicular biopsy. Therefore, we systematically looked to the consequences of the procedure by using clinical observational methods and by modern imaging techniques, respectively. PATIENTS, METHODS: 1874 patients with testicular cancer enrolled in a nation-wide contralateral biopsy study were prospectively analyzed in regard to surgical complications. Serial scrotal imaging was performed by scrotal sonography (7.5 Mhz) in 55 patients and by magnetic resonance tomography (1.5 Tesla machine, surface coil, contrast media) in 60 patients, respectively. Imaging examinations were done preoperatively and again at 1 week, 6 months, 12 months, and 18 months respectively. Imaging results were tabulated according to an abnormality score and analyzed by descriptive statistics. RESULTS: 52 patients (2.78%; 95% confidence intervals 2.05-3.60) experienced surgical complications. Forty minor complications were managed conservatively. Twelve patients (0.64%) required repeat surgery; 1 testicle was ultimately lost following a sequence of unfortunate events. No pre-existing clinical parameter was associated with complications. One week after surgery, abnormalities were detected in 33% by sonography and in 45% by MRI, respectively. Importantly, the abnormalities resolved in 96% of the cases, as found in both of the imaging modalities in the serial scans. CONCLUSIONS: Testicular biopsy is associated with a low burden of clinically significant complications. However, scrotal imaging discloses intratesticular abnormalities in a high proportion of cases one week after the biopsy. These changes represent focal haematoma, oedema or circumscript injury to vascular supply. Most of these lesions resolve with time and are thus not significant, clinically. Evidently, testicular biopsy is a safe procedure provided the vascular anatomy of the testis is respected upon surgery.

Adolescent↗
PubMed2005

Prolonged survival of patients receiving trastuzumab beyond disease progression for HER2 overexpressing metastatic breast cancer (MBC).

BACKGROUND: The aim of this retrospective analysis was to evaluate the impact of trastuzumab-based regimens on the survival of patients with HER2-overexpressing metastatic breast cancer (MBC). The study specifically focussed on the influence of the continuation of trastuzumab-based treatment despite tumor progression on survival. PATIENTS AND METHODS: Patients with HER2 overexpressing MBC were included in this retrospective analysis. HER2 overexpression was determined by the immunohistochemical staining score (DAKO Hercep Test). Trastuzumab was applied at a loading dose of 4 mg/kg and a maintenance dose of 2 mg/kg. RESULTS: Among 136 HER2 overexpressing patients (DAKO score 3+), 66 patients received first-line trastuzumab, 47 patients received trastuzumab as second-line therapy and 23 patients received trastuzumab beyond disease progression. There was no significant difference regarding the duration of trastuzumab-based treatment (first-line: 29.5 weeks vs. second-line: 25 weeks). Moreover, there was no difference in the response rate (first-line: 37.9% vs. second-line: 35.7%) or the median survival (p = 0.47 log rank). Patients who received = 2 trastuzumab-based regimens for MBC survived significantly longer compared to those who had received only 1 regimen (= 2 regimens: 62.4 months vs. 1 regimen: 38.5 months; p = 0.01 log rank). CONCLUSIONS: Trastuzumab is highly effective in the treatment of HER2 overexpressing MBC. Compared to historical controls, overall survival appears to be markedly prolonged, particularly in patients who received sequential trastuzumab-based treatment beyond disease progression.

Adult↗
PubMed2005

Gemcitabine in metastatic breast cancer.

Gemcitabine is a pyrimidine antimetabolite which has shown activity in metastatic breast cancer both as a single agent, but also in various combination regimens. It is characterized by a unique mechanism of action which includes cytotoxic self-potentiation, masked DNA chain termination and potent inhibition of DNA repair. The clinical application of gemcitabine is supported by a favorable toxicity profile. In metastatic breast cancer, several Phase II trials document the activity of gemcitabine in pretreated and unpretreated patients. In a single Phase III trial performed in elderly patients not pretreated, gemcitabine was inferior to epirubicin. High activity has, however, been obtained by the combination of gemcitabine with taxanes such as paclitaxel or docetaxel. In a randomized trial performed in anthracycline-pretreated patients, the combined use of gemcitabine and paclitaxel induced a significant improvement not only of response rate and time to disease progression, but also caused a significant increase in quality of life and survival when compared with paclitaxel alone. The combination of gemcitabine with vinorelbine and cisplatin has been validated in numerous Phase II trials and promises reliable activity in anthracycline- and/or taxane-pretreated patients. Triple-agent regimens such as gemcitabine/epirubicin/paclitaxel provided consistently high response rates in Phase II trials, but failed to show superiority over the 5-fluorouracil/epirubicin/cyclophosphamide regimen in a randomized Phase III trial. Based on high response rates and pathological complete remission rates achieved by preoperative induction therapy with gemcitabine/epirubicin/taxane regimens, ongoing trials focus on the incorporation of gemcitabine into neoadjuvant and adjuvant regimens.

Antimetabolites, Antineoplastic↗
PubMed2004

Effect of chemoradiotherapy with gemcitabine and cisplatin on locoregional control in patients with primary inoperable pancreatic cancer.

Gemcitabine sensitizes tumor cells to radiation and cisplatin and thereby enhances the cytotoxic effect of gemcitabine. Here we report the efficacy and toxicity of concurrent chemoradiation with gemcitabine and cisplatin in the treatment of patients with locally advanced, unresectable pancreatic cancer. A total of 47 patients (29 men, 18 women; median age 61 years) with histologically proven advanced pancreatic carcinoma were included in the study. They underwent chemotherapy with gemcitabine 300 mg/m2 and cisplatin 30 mg/m2 on days 1, 8, 22, and 29; concurrent radiation (45-50 Gy) was applied to the tumor and regional lymph nodes (1.8-2.0 Gy/fraction 5 days per week). Subsequent to chemoradiotherapy, treatment was continued with more two cycles of gemcitabine (1000 mg/m2) and cisplatin (50 mg/m2) applied on days 1 and 15 of a 4-week cycle. After completion of chemoradiotherapy, 9 patients (19.1%) achieved a complete response and 23 patients (48.9%) a partial response, for an overall response rate of 68%. The lesions were considered resectable in 27 patients, and 25 of the 27 patients underwent laparotomy. The other 20 patients underwent a definitive pancreatic resection. Altogether, 13 patients had negative surgical margins. With a median follow-up of 25.7 months (range 12.7-38.7 months) after completion of chemoradiation, distant metastasis had occurred in 23 patients and local recurrence in only 4 of 44 patients (8.5%). the median progression-free survival was 7.8 months (range 6.2-9.4 months). The median survival amounted to 10.7 months (range 8.4-13.0 months) for all patients, whereas it was prolonged to 24.2 months (range 6.8-41.7 months) for those undergoing R0 resection. The main toxicities associated with chemoradiation included grade 3/4 leukopenia (68% of patients) and thrombocytopenia (61%). Episodes of cholangitis were observed in 11 patients. We concluded that gemcitabine and cisplatin can safely be combined with external beam radiation. This preoperative treatment approach is highly effective and appears to improve survival in patients whose tumors are rendered completely resectable.

Adult↗
PubMed2004

Concurrent chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1) resection of locally advanced pancreatic carcinoma.

PURPOSE: To analyze, in a prospective clinical trial, the efficacy and toxicity of concurrent radiotherapy and chemotherapy with gemcitabine and cisplatin in patients with incompletely (R1) resected pancreatic cancer. METHODS AND MATERIALS: Between 2000 and 2002, a total of 30 pancreatic cancer patients were treated. Radiotherapy was performed in 15 patients up to a total dose of 45.0 Gy. An additional 15 patients received a total dose of 50.0 Gy according to the International Commission on Radiation Units and Measurements (ICRU) Report 50 reference point (equivalent to 45.0 Gy at the isodose, including 90% covering the former tumor area and local lymph nodes). Concurrent with radiotherapy, four applications of gemcitabine (300 mg/m(2)) and cisplatin (30 mg/m(2)) were administered. After chemoradiotherapy, patients received four additional courses of gemcitabine (1000 mg/m(2)) and cisplatin (50 mg/m(2)) on Days 1 and 15 in a 4-week cycle. RESULTS: The median progression-free survival was 10.6 months, and the median overall survival was 22.8 months. The 1-, 2-, and 3-year survival rate was 81%, 43%, and 26%, respectively. After completion of chemoradiotherapy, distant metastasis was observed in 14 patients during a median follow-up of 15.0 months (range, 4.6-30.0). One patient developed both local recurrence and distant metastases. Hematologic toxicities were the most prominent side effects (leukopenia Grade 3 and 4 in 53% and 7% and thrombocytopenia Grade 3 and 4 in 33% and 7% of patients, respectively). Grade 3 and 4 GI toxicity was not observed. CONCLUSION: Postoperative chemoradiotherapy with gemcitabine and cisplatin after incomplete (R1) resection of pancreatic carcinoma is safe and feasible. A prolonged progression-free survival suggests high local efficacy, translating into a benefit of overall survival. On the basis of the favorable outcome of patients receiving gemcitabine/cisplatin-based chemoradiotherapy, testing this combined treatment strategy appears warranted in a comparative trial.

Adult↗
PubMed2003

[Radiochemotherapy with gemcitabine and cisplatin in pancreatic cancer -- feasible and effective].

BACKGROUND: Concomitant radiotherapy and chemotherapy with gemcitabine appears to be a promising tool for the treatment of pancreatic cancer since gemcitabine -- applied as single or combination therapy -- proved to have better efficacy in pancreatic cancer than 5-FU containing schemes and furthermore offers radiosensitizing potential. In the present paper our pilot data of concomitant and sequential chemoradiation with gemcitabine and cisplatin are presented. PATIENTS AND METHODS: A total of 57 patients (f/m 23/34) with pancreatic cancer was treated, of whom 33 patients had irresectable tumors, 19 patients following resection (R1 and/or pN+) and five patients with local recurrent disease. Radiotherapy was delivered in 25 fractions up to a total dose of 45.0 Gy specified according to ICRU reference point (50 patients, 1.8 Gy/fraction) respectively 50.0 Gy to gross tumor volume (seven patients; 45.0 Gy in locoregional lymphatic pathways; 2.0/1.8 Gy/fraction). Concomitant with radiotherapy cisplatin (30 mg/m(2)) and gemcitabine (300 mg/m(2)) were applied on days 1, 8, 22 and 29. After simultaneous chemoradiation two sequential cycles gemcitabine and cisplatin (1000 mg/m(2) and 50 mg/m(2) d 1, 15) were applied. RESULTS: With a median follow-up of 8.2 months the median survival time was 14.8 months (irresectable patients: 10.3 months, postoperative patients, 15.1 months). Within 33 irresectable patients 19 and four partial and complete remissions, respectively, were observed. In 14 patients a secondary resection was possible. Using leveled antiemetics with ondansetron and dexamethasone no gastrointestinal toxicities grade III or IV were observed. Hematologic toxicities were the most grave side effects (leukocytopenia III/IV in 29/five patients and thrombocytopenia III/IV in 21/eight patients), however with minor clinical relevancy (one neutropenic infection, one thrombopenic epistaxis). CONCLUSION: The presented treatment scheme using concomitant and sequential gemcitabine and cisplatin with radiation is feasible with justifiable side effects. To evaluate the promising remission and survival rates, randomized trials of neoadjuvant and primary chemoradiation are started.

Adult↗
PubMed2003

Testicular microlithiasis--one case and four points to note.

A 38-year-old man with non-specific scrotal complaints was found to have bilateral testicular microlithiasis (TM) sonographically. MRI of the testes failed to depict microlithiasis. Bilateral double biopsies of the testes revealed testicular intraepithelial neoplasia (TIN; carcinoma in situ of the testis) in only one of the two biopsies from the right testis. At the request of the patient the biopsies were repeated, with the same histological result. A right-sided orchiectomy was performed. Histology disclosed TIN in only some tubules of the lower pole of the testis. This case highlights four interesting points: (i) TM may be associated with testicular malignancy; (ii) MRI does not depict TM; (iii) TIN is arranged focally within the testis; and (iv) a two-site biopsy may increase the sensitivity of the diagnosis of TIN.

Adult↗