Cees H. N. Veenhof

Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group.

OBJECTIVE The survival benefit of adjuvant radiotherapy and 5-fluorouracil versus observation alone after surgery was investigated in patients with pancreatic head and periampullary cancers. SUMMARY BACKGROUND DATA A previous study of adjuvant radiotherapy and chemotherapy in these cancers by the Gastrointestinal Tract Cancer Cooperative Group of EORTC has been followed by other studies with conflicting results. METHODS Eligible patients with T1-2N0-1aM0 pancreatic head or T1-3N0-1aM0 periampullary cancer and histologically proven adenocarcinoma were randomized after resection. RESULTS Between 1987 and 1995, 218 patients were randomized (108 patients in the observation group, 110 patients in the treatment group). Eleven patients were ineligible (five in the observation group and six in the treatment group). Baseline characteristics were comparable between the two groups. One hundred fourteen patients (55%) had pancreatic cancer (54 in the observation group and 60 in the treatment group). In the treatment arm, 21 patients (20%) received no treatment because of postoperative complications or patient refusal. In the treatment group, only minor toxicity was observed. The median duration of survival was 19.0 months for the observation group and 24.5 months in the treatment group (log-rank, p = 0.208). The 2-year survival estimates were 41% and 51 %, respectively. The results when stratifying for tumor location showed a 2-year survival rate of 26% in the observation group and 34% in the treatment group (log-rank, p = 0.099) in pancreatic head cancer; in periampullary cancer, the 2-year survival rate was 63% in the observation group and 67% in the treatment group (log-rank, p = 0.737). No reduction of locoregional recurrence rates was apparent in the groups. CONCLUSIONS Adjuvant radiotherapy in combination with 5-fluorouracil is safe and well tolerated. However, the benefit in this study was small; routine use of adjuvant chemoradiotherapy is not warranted as standard treatment in cancer of the head of the pancreas or periampullary region.

Complications of an implantable venous access device (Port-a-Cath®) during intermittent continuous infusion of chemotherapy

In 149 patients, treated with intermittent continuous infusion of different chemotherapeutic agents, 169 Port-a-Caths were implanted by qualified surgeons and residents in training. The peri- and postoperative complications of implantation of the Port-a-Cath system and the complications during treatment were retrospectively analysed. The Port-a-Cath was in situ for a total of 36247 days (median 181, range 1-1332). Of the 169 catheters, major complications occurred during treatment, with infection in 4 patients (2.4%), occlusion in 3 (1.8%), thrombosis in 8 (4.7%), extravasation in 8 (4.7%) and migration in 3 (1.8%). The peri- and postoperative complication rate was low, although pneumothorax occurred in 6 patients (3.6%). In 25 patients (14.8%) the Port-a-Cath had to be explanted due to complications. It can be concluded that continuous infusion of chemotherapy via a Port-a-Cath system is a relatively safe procedure, although major complications do occur. The experience of the surgeon could not be related to the complications.

DNA double labelling with IdUrd and CldUrd for spatial and temporal analysis of cell proliferation and DNA replication

SummaryA procedure was developed that very effectively distinguishes between IdUrd and CldUrd incorporated in the DNA of cell nuclei and chromosomes. For double staining we used the, rat anti-BrdUrd monoclonal antibody from Sera-lab that binds specifically to CldUrd and BrdUrd but not to IdUrd, in combination with the mouse anti-BrdUrd monoclonal antibody from Becton Dickinson. This antibody binds to all three halogenated deoxyuridines, but when the nuclei are washed in TRIS buffer with a high salt concentration the antibodies linked to CldUrd-labelled DNA are removed. When analysing the effect of the deoxyuridines on the cell cycle we found that the growth kinetics of Chinese hamster cells were not changed by adding IdUrd or CldUrd for 30 min at a concentration of 10 μm, whereas adequate double labelling required only 2 min pulses. The effectiveness of the technique was demonstrated in two model experiments. The first test concerned the assessment of cell recruitment in the central areas of slow-growing clones, after addition of fresh medium. The second experiment focussed on the spatial resolution of the method. Double-labelled metaphase chromosomes showed interspersed green and red replication bands with a spacing corresponding with medium resolution Giemsa banding patterns.

Feasibility and efficacy of high dose conformal radiotherapy for patients with locally advanced pancreatic carcinoma.

The feasibility and efficacy of high dose conformal radiotherapy were examined in the treatment of patients with locally advanced, unresectable pancreatic carcinoma.

Phase II trial of weekly locoregional hyperthermia and cisplatin in patients with a previously irradiated recurrent carcinoma of the uterine cervix

The biologic rationale for combining cisplatin with locoregional hyperthermia (HT) relates to the potentiating effect of HT on cisplatin cytotoxicity.

Metastatic tumors to the orbit―management and prognosis

In a retrospective study the records of 34 consecutive cases with tumors metastatic to the orbit were reviewed with special attention to the management and prognosis of these patients. The primary tumor site was the breast in 20 patients, prostate in 5, kidney in 2 and skin in 2. The remaining 5 patients had other primary tumour sites. The symptoms of orbital metastasis preceded the detection of the primary tumor in 8 cases (24%). Twenty patients died after a mean interval of 25 months following the diagnosis of the orbital metastasis. This study gives a summary of the clinical features of these patients. With improved methods of treatment it was possible to obtain a relief of orbital symptoms in 24 patients (71%). Although the life expectancy of these patients remains poor, treatment can result in symptomatic relief and in an improvement in the quality of life, which is the main goal in the management of these patients.

Interleukin-6 concentrations in the serum of patients with AIDS-associated Kaposi's sarcoma during treatment with interferon-alpha

Abstract. Interleukin‐6 (IL‐6) levels were determined in the serum of 14 HIV‐1‐infected patients with Kaposis sarcoma. 10 HIV‐1‐infected patients without symptoms, and 10 healthy male subjects. IL‐6 levels were also determined in the serum of the 14 patients with Kaposis sarcoma during treatment with high‐dose human recombinant interferon‐alpha (IFNα). Serum IL‐6 levels were significantly higher in the patients with Kaposis sarcoma than in the HIV‐infected patients without symptoms and the controls. There was no consistent pattern of changes of IL‐6 levels during IFNα treatment. These results support the view that IL‐6 is a cytokine involved in the pathogenesis of AIDS‐associated Kaposis sarcoma, but appear to argue against an effect of IFNα on the production or release of IL‐6 as an important mechanism of action of IFNα.

Combined zidovudine and interferon‐alpha treatment in patients with AIDS‐associated Kaposi's sarcoma

Abstract. The effectiveness of addition of interferon‐alpha (IFN‐alpha) to zidovudine in patients with AIDS‐associated Kaposis sarcoma was assessed in a non‐randomized, phase II clinical trial. Twenty‐one patients were treated with oral zidovudine (600 mg daily) and IFN‐alpha (9 MU subcutaneously daily) for 8 weeks. In patients with progressive disease, IFN‐alpha was increased to 18 MU daily for another 4 weeks. Only one of the 20 evaluable patients achieved a partial response at 8 weeks, that lasted for 3 months. Despite IFN‐alpha dose escalation in six patients, no further responses were seen. While myelotoxicity was mild, fatigue was the dose‐limiting side‐effect that prevented dose escalation in seven eligible patients. The combined treatment did not result in a decrease in HIV‐Ag. In summary, our results indicate that the addition of IFN‐alpha to zidovudine in patients with AIDS‐associated Kaposis sarcoma is not an efficacious treatment.

Comparison of Renal Function Parameters in the Assessment of cis-PIatin Induced IMephrotoxicity

The early renal function parameters (RFP), i.e. urinary alanine aminopeptidase (AAP), beta-galactosidase (beta GAL), N-acetyl-beta-D-glucosaminidase (NAG), retinol-binding protein (RBP), albumin (ALB), total protein (TP) and the conventional RFP plasma creatinine were assessed in 8 patients before and during treatment with the nephrotoxic antitumor agent cis-platin. Plasma creatinine increased during treatment with cis-platin. In all patients, acute tubular damage was revealed by early RFP. Albumin and total protein excretion patterns suggested alterations in glomerular function. The cumulative change in RBP excretion was related to plasma creatinine concentrations following cis-platin administration. The present study demonstrates that urinary RBP is a valuable parameter for the early assessment of cis-platin-induced nephrotoxicity.

A dose-escalation study of recombinant interferon-alpha in patients with a metastatic carcinoid tumour

The efficacy of interferon alpha-2b in doses up to 12 x 10(6) IU three times weekly was studied in 21 patients with a metastatic carcinoid tumour. Of these 21 patients, 19 were evaluable for response. Patients were treated with escalating dosages of interferon alpha-2b: 3 x 10(6) IU, 6 x 10(6) IU and 12 x 10(6) IU. The escalation was performed every 8 weeks when no objective tumour regression was observed. Patients were also evaluated for biochemical response and symptomatic improvement. One objective tumour regression was observed. Of the 15 patients with elevated 5-hydroxyindole acetic acid (5-HIAA) excretion, 5 (33%) had a more than 50% decrease in 5-HIAA excretion. Relief of symptoms occurred in 11 patients (58%). This improvement was already apparent during the initial 8 weeks of treatment. Increasing the dose to 6 or 12 x 10(6) IU interferon alpha-2b did not result in further symptomatic improvement. In contrast toxicity was considerable with the higher dosages of interferon alpha-2b. It is concluded that low dose interferon alpha-2b (3 x 10(6) IU) three times weekly is as effective as higher dosages of interferon alpha-2b at ameliorating symptoms of the carcinoid syndrome.