Variation at presentation among colon cancer patients with metastases: a population-based study.

AIM: The study aimed to describe and follow a 2 year cohort of colon cancer patients with Stage IV disease from presentation to long-term outcome. METHOD: The records of 177 colon cancer patients diagnosed in southeast Sweden during 2009-2010 with disseminated disease at presentation were reviewed retrospectively. RESULTS: The patients were heterogeneous with respect to age, performance status and survival. Despite metastatic disease, local symptoms from the primary tumour dominated the initial clinical picture. Forty-one per cent had anaemia. The time from suspicion of colon cancer to established diagnosis of disseminated disease varied from 0 to 231 days (emergency cases included, median 12 days). The majority (77%) were diagnosed in hospital. In 53% the primary tumour and the metastases were not diagnosed on the same occasion which may increase the risk for misinformation or delays in the care process. The possibility of simultaneous diagnosis was doubled when the patient was investigated as an inpatient. Patients were seen by one to 12 physicians (median three) in the investigation phase, and one to 47 (median 11) from diagnosis until the last record in the hospital notes. The 1-year survival was 46%. CONCLUSION: Patients with metastatic colon cancer at presentation are heterogeneous and warrant an adapted multidisciplinary approach to achieve the goal of individualized treatment for each patient in accordance with the Swedish national cancer strategy.

Chronomodulated capecitabine in combination with short-time oxaliplatin: a Nordic phase II study of second-line therapy in patients with metastatic colorectal cancer after failure to irinotecan and 5-flourouracil.

BACKGROUND: Oxaliplatin in combination with capecitabine prolongs survival in patients with metastatic colorectal cancer (mCRC). Chronomodulation might reduce toxicity and improve efficacy. PATIENTS AND METHODS: A phase II study examining chronomodulated XELOX(30) (XELOX(30chron)): oxaliplatin: 130 mg/m(2) on day 1, as a 30-min infusion between 1 and 3 p.m. Capecitabine: total daily dose of 2000 mg/m(2), 20% of the dose between 7 and 9 a.m. and 80% of the dose between 6 and 8 p.m. in patients with mCRC resistant to irinotecan. Seventy-one patients were enrolled. Response rate was 18%; median progression-free survival 5.1 months and median overall survival (OS) 10.2 months. Platelet count and performance status were significantly correlated to OS in multivariate analyses. Neurotoxicity grade 2 and 3 was seen in 25% and 2% of patients, respectively, other grade 3 toxic effects were as follows: nausea 6%, vomiting 3%, diarrhoea 12% (3% experienced grade 4) and palmoplantart erytem 9%. CONCLUSION: XELOX(30chron) is a convenient second-line regimen with efficacy and safety profile similar to other oxaliplatin schedules. To further investigate chronomodulated XELOX, we have started a Nordic randomised phase II study comparing XELOX(30) and XELOX(30chron) as first-line therapy in patients with mCRC.

A randomized phase III multicenter trial comparing irinotecan in combination with the Nordic bolus 5-FU and folinic acid schedule or the bolus/infused de Gramont schedule (Lv5FU2) in patients with metastatic colorectal cancer.

BACKGROUND: To compare irinotecan with the Nordic 5-fluorouracil (5-FU) and folinic acid (FA) bolus schedule [irinotecan 180 mg/m(2) on day 1, 5-FU 500 mg/m(2) and FA 60 mg/m(2) on day 1 and 2 (FLIRI)] or the Lv5FU2 schedule [irinotecan 180 mg/m(2) on day 1, FA 200 mg/m(2), 5-FU bolus 400 mg/m(2) and infused 5-FU 600 mg/m(2) on day 1 and 2 (Lv5FU2-IRI)] due to uncertainties about how to administrate 5-FU with irinotecan. PATIENTS AND METHODS: Patients (n = 567) with metastatic colorectal cancer were randomly assigned to receive FLIRI or Lv5FU2-IRI. Primary end point was progression-free survival (PFS). RESULTS: Patient characteristics were well balanced. PFS did not differ between groups (median 9 months, P = 0.22). Overall survival (OS) was also similar (median 19 months, P = 0.9). Fewer objective responses were seen in the FLIRI group (35% versus 49%, P = 0.001) but the metastatic resection rate did not differ (4% versus 6%, P = 0.3). Grade 3/4 neutropenia (11% versus 5%, P = 0.01) and grade 2 alopecia (18% versus 9%, P = 0.002) were more common in the FLIRI group. The 60-day mortality was 2.4% versus 2.1%. CONCLUSIONS: Irinotecan with the bolus Nordic schedule (FLIRI) is a convenient treatment with PFS and OS comparable to irinotecan with the Lv5FU2 schedule. Neutropenia and alopecia are more prevalent, but both regimens are equally well tolerated.

Short-time infusion of oxaliplatin in combination with capecitabine (XELOX30) as second-line therapy in patients with advanced colorectal cancer after failure to irinotecan and 5-fluorouracil.

BACKGROUND: The efficacy of oxaliplatin combined with capecitabine (XELOX) as second-line therapy in patients with advanced colorectal cancer (ACRC) resistant to irinotecan is not well established. Oxaliplatin induces acute, cold-induced neuropathy in most patients. The incidence is claimed to be infusion rate-dependent and therefore a 2-h infusion is recommended. PATIENTS AND METHODS: For practical and economic reasons, but also for patient's convenience, we performed a phase II study to examine XELOX30 (capecitabine 1000 mg/m2 orally twice daily on days 1-14 and oxaliplatin 130 mg/m2 as a 30 min infusion on day 1) in patients with ACRC resistant to irinotecan. In addition the pharmacokinetics of oxaliplatin was studied. RESULTS: From November 2002 to September 2003, 70 patients with ACRC were treated with XELOX30. Median age was 62 (range 33-74 years) years and median performance status was 1 (range 0-2). The median number of courses was four (range 1-12) and median cumulative dose of oxaliplatin was 530 (range 125-1560) mg/m2. The response rate was 17% (95% CI 10-23), median time to progression (TTP) was 5.4 months (95% CI 4.6-6.4) and median survival 9.5 months (95% CI 8.5-11.2). White blood cell count (WBC) and performance status were significantly correlated to TTP. Neurotoxicity was moderate: grade 1 56%, grade 2 17% and grade 3 6%. Other grade 3 toxicities were nausea/vomiting 9%, diarrhoea 14% and PPE 8%. The maximum blood concentration and total body clearance of oxaliplatin was higher than previously reported in studies examining 2-h infusions, but the volume of distribution and terminal half-life was in close agreement with previous results. CONCLUSION: XELOX30 is a very convenient second-line regimen in ACRC with an activity and safety profile similar to other oxaliplatin schedules.

Cancer patients hospitalised for palliative reasons. Symptoms and needs presented at a university hospital.

The aim of this study was to identify patients in need of palliative care in 11 different care units with a total of 256 beds at Linköping University Hospital and to look at their overall situation with respect to assessed symptom control and quality of life. There were 46 patients fulfilling the two criteria of incurable cancer and need for palliative care, and each was assessed with the aid of a questionnaire (five oral questions on life situation) and a single visual analogue scale (VAS) about their overall quality of life (QoL). Each patient also assessed him- or herself on the Edmonton Symptom Assessment Scale (ESAS). Total ESAS scores ranged from 20 to 639 mm (median 211). Median VAS scores (100 mm = greatest symptom severity) were as follows: nausea 6 mm, pain 9 mm, anxiety 17 mm, depression 18 mm, drowsiness 35 mm, activity 38 mm, appetite 45 mm, and sensation of well-being 46 mm. The median score for QoL was 47 and correlated well with the total ESAS score. Thirty-seven patients answered the open question "What in your current situation troubles you the most?". Seven patients answered "nothing", and 10 said "the present symptoms". Twenty patients had different concerns (existential, social, and psychological). The low number of hospitalised patients found reflects a well-functioning hospital-based home-care unit. Reduced appetite, sensation of well-being and activity were dominant, while pain and nausea were less intense. The simple QoL-VAS seemed to be comparable to ESAS, which is more useful for assessing each single symptom. The non-physical dimensions need more attention in the future in order to achieve totally satisfactory palliative care.

A phase II study of irinotecan alternated with five days bolus of 5-fluorouracil and leucovorin in first-line chemotherapy of metastatic colorectal cancer.

PURPOSE: This multicenter phase II study was designed to assess the efficacy of the alternating schedule of irinotecan (CPT-11) with bolus 5-fluorouracil (5-FU) and leucovorin (LV) in first-line chemotherapy for metastatic colorectal cancer (CRC). PATIENTS AND METHODS: Patients with histologically proven metastatic colorectal cancer, and at least one bidimensionally measurable lesion, aged 18-70, with performance status < or = 2, normal baseline biological values and no prior chemotherapy (or only adjuvant chemotherapy completed > or = 6 months before study entry) were selected. Treatment was irinotecan 350 mg/m2, i.v., day 1, alternating with leucovorin 20 mg/m2 i.v. and 5-FU 425 mg/m2, i.v. daily for five consecutive days, day 22-26 (Mayo Clinic regimen). One alternating cycle was to be performed every six weeks. Patients were evaluated for efficacy every alternating cycle. Treatment was administered until five alternating cycles, disease progression, unacceptable toxicity or patient refusal. RESULTS: Thirty-three patients (28 chemotherapy-naïve and five with prior adjuvant treatment completed > 1 year prior to accrual) were enrolled. The objective response rate (RR) was 30% (95% CI: 16-49; 10 patients/33; nine partial response and one complete response). All responses were reviewed by an independent external review committee. An additional 49% of patients had stable disease. The median survival was 16 months, the one year survival amounted to 58% and the median progression free survival was 7.2 months. Relative dose intensity was nearly 90% for both drugs. Grade 3-4 diarrhea and neutropenia were the most frequent severe toxic events, seen in 24% and 64% of patients, respectively. CONCLUSIONS: The alternating schedule of CPT-11 350 mg/m2 with five days bolus of 5-FU and low dose LV is an active and feasible regimen as front-line therapy for metastatic CRC. It is well tolerated, without evidence of overlapping toxicity. The response rate appears promising with regard to that expected with either single agent. This regimen warrants further assessment in randomized trials.

Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer.

BACKGROUND: In phase II studies, irinotecan is active in metastatic colorectal cancer, but the overall benefit has not been assessed in a randomised clinical trial. METHODS: Patients with proven metastatic colorectal cancer, which had progressed within 6 months of treatment with fluorouracil, were randomly assigned either 300-350 mg/m2 irinotecan every 3 weeks with supportive care or supportive care alone, in a 2:1 ratio. FINDINGS: 189 patients were allocated irinotecan and supportive care and 90 supportive care alone. The mean age of the participants was 58.8 years; 181 (65%) were men and 98 (35%) were women. WHO performance status was 0 in 79 (42%) patients, 1 in 77 (41%) patients, and 2 in 32 (17%) patients. Tumour-related symptoms were present in 134 (71%) patients and weight loss of more than 5% was seen in 15 (8%) patients. With a median follow-up of 13 months, the overall survival was significantly better in the irinotecan group (p=0.0001), with 36.2% 1-year survival in the irinotecan group versus 13.8% in the supportive-care group. The survival benefit, adjusted for prognostic factors in a multivariate analysis, remained significant (p=0.001). Survival without performance-status deterioration (p=0.0001), without weight loss of more than 5% (p=0.018), and pain-free survival (p=0.003) were significantly better in the patients given irinotecan. In a quality-of-life analysis, all significant differences, except on diarrhoea score, were in favour of the irinotecan group. INTERPRETATION: Our study shows that despite the side-effects of treatment, patients who have metastatic colorectal cancer, and for whom fluorouracil has failed, have a longer survival, fewer tumour-related symptoms, and a better quality of life when treated with irinotecan than with supportive care alone.

Infradiaphragmatic Hodgkin's disease: the Swedish National Care Programme experience. The Swedish Lymphoma Study Group.

A Swedish national care programme has provided guidelines for staging, treatment and follow-up of all patients with Hodgkin's disease (HD) since 1985. Between January 1985 and December 1992, 920 patients were reported and followed prospectively. Of a total of 533 patients with stage I and II disease, 484 presented with supradiaphragmatic HD and 49 (9%) with infradiaphragmatic HD. The median follow-up time was 4.3 yr (3.3-10 yr). Significant differences in average age (45 +/- 21 yr and 55 +/- 19 yr), male:female ratio (1.1:1 and 2.8:1) and B-symptoms (25% and 47%) were observed in patients with supra- and infradiaphragmatic HD, respectively. Forty-six patients with infradiaphragmatic HD were treated with a curative intention and 40 (87%) achieved a complete response. Eleven (28%) of the 40 patients have recurred and 8 patients have died of HD. Complete response rates and recurrence frequencies did not differ from those observed in patients with supradiaphragmatic HD. Mortality was, however, significantly higher (p = 0.001) in the infradiaphragmatic group; this was due mainly to poorer effects of salvage treatment in a elderly population. In this population-based study, patients with peripheral disease in stage IA respond well to inverted Y irradiation alone, whereas it appears to be important to give stage II patients chemotherapy or a combined modality treatment in order to avoid unacceptably high recurrence rates.

Risk-adapted treatment of clinical stage 1 non-seminoma testis cancer.

250 patients with clinical stage 1 non-seminomatous germ cell tumours of the testis (NSGCT 1) were included into a prospective multicentre protocol during 1990-1994 and treated according to three risk strata: patients without tumour cell invasion of vascular structures in the testis (VASC-) and elevated serum AFP levels (AFP+) at orchiectomy were considered low risk (LR) and only observed closely. VASC- and AFP- or VASC+ and AFP+ patients were presumed intermediate risk (IR) and pathologically staged (PS) by retroperitoneal lymph node dissection (RPLND). VASC+ and AFP-patients were regarded as high risk (HR) and received adjuvant chemotherapy (PEB x 3). At a median observation time of 40 (7-68) months, all patients were alive and without evidence of active germ cell cancer. The actuarial relapse rate in the 106 LR patients was 22%, and 70% (14/20) had elevated serum tumour markers at relapse. One of 32 (3%) HR patients relapsed with a resectable retroperitoneal mature teratoma despite adjuvant chemotherapy. Only 14% of the 99 IR patients who underwent RPLND had PS2 disease, and the actuarial relapse rate in 85 PS1 patients was 18%. This multicentre study demonstrated that excellent therapeutic outcome is possible when 18 comparatively small urological and oncological centres follow a strict and formal cancer care programme. The useful prognostic effect of VASC was once again verified. Pathological staging by RPLND in NSGCT1 is, in our opinion, not necessary, with presumed low-risk patients offered surveillance and high-risk patients offered adjuvant chemotherapy.

Central venous catheter placement using electromagnetic position sensing: a clinical evaluation.

A critical step in placing a central venous catheter (CVC) is positioning the catheter tip in a location just outside the heart in the lower superior vena cava. The authors report the clinical evaluation of a new commercially available system that uses electromagnetic technology to sense the position of a catheter tip during CVC insertion. Fifty catheters were implanted using fluoroscopy to monitor system accuracy. The catheters were accurately placed (within 2.5 cm of the desired optimal position) in 46 of the 50 cases (92%). In two patients with abnormal chest geometry (short, barrel chests), catheter tip location was difficult to determine. In two other cases, procedural difficulties unrelated to the system (difficulty in external landmark determination and unclear fluoroscopic view of the optimal position) resulted in catheter placement outside the targeted range. The electromagnetic system provides an opportunity to eliminate "blind" CVC placement procedures and to reduce or omit perioperative fluoroscopy of x-ray during CVC insertion.

Determination of urinary 8-hydroxydeoxyguanosine by automated coupled-column high performance liquid chromatography: a powerful technique for assaying in vivo oxidative DNA damage in cancer patients.

An automated analytical method has been developed for determination of the oxidative DNA adduct, 8-hydroxydeoxyguanosine (8OHdG) in human urine, based on coupled-column high performance liquid chromatography with electrochemical detection. Urine is concentrated on Bondelut CH by means of an automated sample processor, and the enriched sample injected on to a polymeric reversed phase column coupled in line with an electrochemical detector and a C18 reversed phase column. By use of the electrochemical detector, a suitable retention time interval is set for collection of the fraction containing 8OHdG from the chromatography on the first column; this fraction is collected in a 2 mL loop and injected onto the C18 column. The system is operated by an automatic valve station controlled by an integrator. The method has a large sample capacity and measures 31.1, 15.7, and 7.43 nmol 8OHdG/L urine with variation coefficients of 8, 8 and 24% within series and 8, 11 and 23% between series. Normal healthy individuals were found to excrete 14.9 +/- 7.8 nmol 8OHdG/24 h, or 1.11 +/- 0.62 mumol 8OHdG per mol creatinine, in their urine, whereas increased levels of 8OHdG were found in 24 h collections from a variety of cancer patients, both in samples taken before onset of oncological therapy (1.84 +/- 1.12 mumol/mol creatinine, P < 0.01 versus healthy individuals) and after therapy onset (2.18 +/- 1.44 mumol/mol creatinine, P < 0.001 versus healthy individuals). Moreover, mean values of 8OHdG in random urinary samples from cancer patients were significantly higher than from healthy individuals (2.42 +/- 2.28 versus 1.19 +/- 0.48 mumol/mol creatinine, P < 0.001), both in samples taken before therapy onset (1.91 +/- 0.96, P < 0.001 versus healthy individuals) and after (2.57 +/- 2.46, P < 0.001 versus healthy individuals). High levels of urinary 8OHdG were found in patients subjected to whole body irradiation, and in patients receiving chemotherapy with various cytostatic agents. The potential use of the method for detecting increased urinary 8OHdG excretion and conditions associated with increased oxidative DNA damage in humans is discussed.

Implantable devices for venous access: nurses' and patients' evaluation of three different port systems.

Implantable injection port systems are safe and convenient for long-term venous access. The present investigation comprises nurses' and patients' evaluation of three different types of devices; Port-A-Cath (16.0 g), Cordis Miniport (3.8 g) for implantation in the chest wall and the PAS Port system (5.6 g) for implantation in the forearm. The devices were implanted for chemotherapy. Eighty patients and 17 nurses answered a questionnaire regarding their experience with the devices. Overall, the systems functioned well and were helpful for both patients and nurses. In the patient study few significant differences emerged. Nurses noted that the PAS Port system was more difficult to withdraw blood from (P < 0.001) and its infusion flow capacity was inferior to the two ports in the chest wall (P < 0.001). Port-A-Cath was judged to be the easiest system for needle insertion and the needle position was felt to be more secure (P < 0.001). Fourteen of the 17 nurses preferred Cordis Miniport for cosmetic reasons (P < 0.001). All devices functioned well. The differences in shape, size and site of implantation allow an optimum port selection for each patient. The replies in this study expressed the need for educational programmes in order to spread the injection port concept further.

Fibrin sleeve formation after long term brachial catheterisation with an implantable port device. A prospective venographic study.

OBJECTIVE: To evaluate the risk of thrombosis after long term venous access with an implantable port device (PAS-Port system). DESIGN: Open study. SETTING: University Hospital, Linköping, Sweden. SUBJECTS: Sixteen patients who required central venous catheters for long term chemotherapy were prospectively followed for 218 patient months (median 12.5 months/patient, range 3-34). INTERVENTIONS: Venogram taken while the catheters were being withdrawn. Venography was also done in 10 patients 1-29 months after the catheter had been removed. RESULTS: The venograms showed that fibrin sleeves had developed along the route of the catheter in all cases (cubital vein to the superior vena cava n = 7; to subclavian vein alone n = 8; and basilic vein alone n = 1). One of the 10 patients who underwent venography 1-29 months later had developed an occlusive subclavian vein thrombosis with well developed collateral vessels 10 months after the catheter had been removed. CONCLUSION: Because of the high incidence of formation of extensive fibrin sleeves, implantable port devices should be removed as soon as they have served their purpose. If catheters malfunction they should be evaluated radiographically.

Cath-Finder Catheter Tracking System: a new device for positioning of central venous catheters. Early experience from implantation of brachial portal systems.

To simplify the implantation procedure of a new brachially implantable venous access system (P.A.S. Port. Pharmacia Deltec Inc., St. Paul, MN, USA), the Cath-Finder Catheter Tracking System (Pharmacia Deltec) was evaluated. The Cath-Finder senses the catheter tip position by utilizing a preconnected sensor wire (guidewire) within a catheter to detect an electromagnetic signal transmitted through the body tissue from a locator wand positioned over an appropriate external landmark. The aim of the study was to evaluate the accuracy of the Cath-Finder (compared to fluoroscopy) in determining the catheter tip position peroperatively during implantation of P.A.S. Port systems in patients with malignant diseases. The accuracy of the Cath-Finder in assessing the position of the catheter tip was registered in 16 implantation procedures. The tip positions determined with the Cath-Finder (when projected on the skin) correlated well to fluoroscopy (within 1 cm in eleven patients, 2-3 cm in four patients, and 4 cm in one patient). By using the right 3rd rib parasternally as an external landmark for the locator wand, the Cath-Finder Catheter Tracking System appears to be an alternative to fluoroscopy peroperatively for accurate placement of central venous catheters in the superior vena cava. However, a postoperative confirmatory x-ray control is recommended until further experience of the system is available.

A new injection portal for brachially inserted central venous catheter. A multicenter study.

Totally implantable portal systems are widely used for long-term central venous access. A new venous portal system inserted via the brachial veins (P.A.S. Port system, Pharmacia Deltec Inc, U.S.A.) was studied in five centres. From January 1988 through May 1989 61 systems were implanted. Fifty-two patients had malignant diseases. Nine cases had non-malignant disorders. The portals were implanted subcutaneously in the fore-arm and catheterization was done percutaneously (46) or by cutdown-technique (15) under local anesthesia. Catheter tip position was controlled by fluoroscopy or x-ray. The basilic vein (49) and the cephalic vein (12) were used. The total follow-up time for all systems was 323 months. Forty-five systems were still in use at the end of the observation period, six were explanted electively at the end of infusion therapy and six systems were still functioning at the time of the patient's death (at a maximum of 14 months after implantation). Temporary armphlebitis was noticed on the first postoperative week in five patients. Two P.A.S. Port systems were explanted due to infection and one because of skin rupture at the wound. One intact system was removed as it was thought to be leaking because of needle displacement. The P.A.S. Port system is easy and safe to implant with a high success rate and a low complication rate. It is well accepted by patients and nurses. The device should be advantageous in patients unsuitable for standard venous portal systems and offers an excellent alternative system for venous access.

Effect of microspheres in intra-arterial chemotherapy. A study of arterio-venous shunting and passage of a labelled marker.

Degradable starch microspheres (DSM) mixed and injected with a cytostatic drug might improve intra-arterial chemotherapy by increasing the local drug concentration. Several factors are of importance for an optimal effect of the microspheres, e.g. size and vascularity of the tumour, arterial blood flow and arterio-venous shunts. Therefore, the dose of DSM has to be individualized. A method for continuous monitoring of the effect of DSM was developed. A radiolabelled marker was injected intra-arterially mixed with DSM and mitomycin C. Two kinetic parameters--Passing Fraction and Marker Flow Rate--were found to be influenced by the microspheres and thus seemed to be useful for monitoring the DSM-treatment. Arterio-venous shunting was measured as passage of 99Tcm-labelled macroaggregated albumin through the liver to the lungs. Significant increase of shunting after injection of DSM was demonstrated in 15 out of 19 patients. Almost no effect of the microspheres was seen in patients with marked arterio-venous shunting or minimal reduction of the marker flow rate, but in others the passage of the labelled marker could generally be significantly reduced.

Effect of portal blood flow and intra-arterially injected starch microspheres on the passage of a labelled tracer through the liver. An experimental study in pigs.

Pig liver was used to study the influence of portal blood flow and degradable starch microspheres (DSM) on the passage of radiolabelled methylene-di-phosphonate from the hepatic artery to the systemic circulation. When the portal vein was clamped abut 70 per cent of the labelled marker injected into the hepatic artery passed to the systemic circulation and the remaining 30 per cent passed when the portal vein was opened. When the flow of the hepatic artery was stopped, the portal blood flow alone drained about 65 per cent of the marker, which was given as a small volume injection into the hepatic artery. When both the arterial perfusion and the portal blood flow were closed the marker only slowly passed to the systemic circulation. DSM injected into the hepatic artery reduced the passage of the marker through the liver to 75 per cent of the reference level when the portal vein was open. When it was clamped this figure was reduced to about 25 per cent. The effect of DSM on the passage of the labelled marker was found to be dose dependent. It is suggested that the reduced passage of a labelled tracer given mixed with DSM is a useful measure of degree of arterial occlusion in the liver. However, because of the drainage via the portal system the passage cannot be completely inhibited.

Effect of starch microspheres on the passage of labelled erythrocytes and a low molecular weight marker through the liver.

Degradable starch microspheres (DSM) injected intra-arterially together with cytostatic drugs increase the regional uptake of the drug and as a result reduce the systemic drug concentration. Previous studies have indicated that fixed doses of DSM result in different degrees of vascular occlusion and therefore variable systemic concentration of the co-injected drug. Continuous registration of the systemic concentration of 99Tcm-hydroxymethylene diphosphonate (99Tcm-HDP) co-injected intra-arterially with DSM was earlier used to monitor treatment sessions and to optimize the dose of microspheres. Further to investigate the mechanism of DSM-induced retention, the effect of DSM on the passage of this low molecular weight marker and of labelled erythrocytes (a marker confined to the blood vessels), was compared in 10 patients with liver metastases. DSM reduced the amount of 99Tcm-HDP passing through the liver by 6 to 47 per cent while the amount of erythrocytes eventually passing the liver was much less reduced (0-14%). The rate of passage, however, was significantly reduced for both labelled markers. These results indicate that substances retained by co-injection of DSM are not to a significant extent lodged within the blood vessels but diffuse into extra-vasal tissue compartments.

Intra-arterial mitomycin C treatment of unresectable liver tumours. Preliminary results on the effect of degradable starch microspheres.

Regional chemotherapy might be more efficient if the cytostatic drug is injected together with degradable starch microspheres (DSM), which induce temporary blockage of arterioles and trap the co-injected drug in tumour. Eighteen patients with non-resectable liver cancer were included. Mitomycin C (15 mg/m2) was injected intra-arterially mixed with 900 mg of DSM every six weeks. For estimation of the effect of DSM in the liver a radiolabelled tracer was injected via the same route. Its passage through the liver to the systemic circulation was continuously measured by a detector situated over peripheral blood vessels. The effect of DSM on the tracer passage varied considerably between different patients. The study also indicated opening of new vascular pathways some minutes after the initial injection. The dose of DSM for total blockage of the arterial blood flow, indicated by angiography, also varied. In some patients 540 mg induced total occlusion. In others neither angiographic nor tracer passage were affected by the microspheres although 900 mg (or even more) were injected. Factors such as size of the vascular bed, portal and arterial blood flow and arterio-venous shunting seemed to be of great importance and should be controlled in order to optimize the use of DSM in conjunction with chemotherapy of liver tumours.