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J Verweij

Publications and source records attributed to J Verweij.

At least 235 records · Page 13Linked to original sources
PubMed1996

Clearance of neurotransmitter from the cone synaptic cleft in goldfish retina.

Dendrites of bipolar and horizontal cells protrude deeply into the synaptic terminals of cones in goldfish retina. This arrangement gives the impression that the cone synaptic terminal surrounds a morphologically shielded compartment, the cone synaptic cleft, from which clearance of neurotransmitter by diffusion is limited. In this study the time constant of this clearance has been approached in two ways: (1) the morphological parameters determining the clearance (extracellular synaptic volume and leak area), were estimated using morphometric methods. These data were introduced into a diffusion model of the cone pedicle, yielding a time constant for the clearance of < 1 msec; (2) the time constant of the light onset response when the glutamate transporter in the cone was blocked with DL-threo-beta-hydroxyaspartate or dihydrokainate, was interpreted as the time constant of the clearance, yielding values of almost 650 msec compared to around 90 msec in control conditions. The decay time-constant of the Ca-dependent tail-currents in cones was used, as an approximation of the dynamics of the intracellular Ca-concentration and thus of the glutamate release by the cones. The decay time constant was about 800 msec. This suggests that the intracellular Ca-concentration in the synaptic terminal and hence the glutamate release by the cones drops with a similar large time constant. These results indicate that the cone pedicle in goldfish does not limit the clearance of neurotransmitters from the synaptic cleft and that the fast light onset response of horizontal cells under control conditions is due to activation of glutamate transporters by hyperpolarization of the cone membrane potential while the glutamate release drops slowly. The slow horizontal cell light onset response in beta-hydroxyaspartate or dihydrokainate may be due to a slow reduction of the glutamate release by the cones at light onset.

Animals↗
PubMed1996

Horizontal cells feed back to cones by shifting the cone calcium-current activation range.

We studied feedback from horizontal cells to cones in isolated goldfish retinae and found that surround stimuli evoke an inward current and a slowly developing outward current. The surround-evoked currents are blocked by the glutamate antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) and are, like horizontal cell responses, most effectively evoked by large stimuli. This indicates that the currents are caused by feedback from horizontal cells. The surround-evoked inward current is neither blocked by picrotoxin nor carried by chloride. Instead, it is carried by calcium, and it triggers a slowly developing calcium-dependent chloride current. We were unable to mimick the surround-evoked currents by modulating the extracellular GABA concentration. We conclude that when horizontal cells hyperpolarize they feed back to the cones by shifting the cone calcium-current activation range to more negative potentials. This type of feedback, directly targeted at the calcium current, scarcely influences the membrane potential of the receiving neuron, but effectively modulates its synaptic output.

Animals↗
PubMed1996

Modulation of horizontal cell receptive fields in the light adapted goldfish retina.

In the isolated goldfish retina, 700 nm background illumination increases the horizontal cell receptive field size, as measured with 565 nm slits of light, but decreases the receptive field size, when measured with 660 nm slits. These background-induced changes in receptive field size are absent when the depolarizing responses in bi- and triphasic horizontal cells are blocked by lowering the [Ca2+] in the Ringer's solution from 1.0 to 0.1 mM. These results cannot be explained by the linear properties of the horizontal cell layers, nor by slow adaptational processes, but are consistent with the concept that feedback from horizontal cells to cones modifies the horizontal cell receptive field properties.

Adaptation, Ocular↗
PubMed1996

Phase I and pharmacological study of the new topoisomerase I inhibitor GI147211, using a daily x 5 intravenous administration.

Topoisomerase I inhibitors are interesting anti-cancer agents with a novel mechanism of action. We performed a phase I study with intravenous GI147211, a new semisynthetic camptothecin analogue, using a daily x 5 schedule administered every 3 weeks, to evaluate the side-effects and pharmacokinetics of the agent. Patients with a histologically confirmed diagnosis of a solid tumour refractory to standard froms of therapy were eligible for the study. GI147211 was given as a 30 min intravenous infusion daily for 5 consecutive days, repeated every 3 weeks. In subsequent patient cohorts the dose was escalated from 0.3 to 1.5 mg m-2 day-1. Pharmacokinetics analysis was performed on days 1 and 4 of the first course using a validated high-performance liquid chromatographic assay and non-compartmental methods. A total of 19 patients were entered into the study, one patient was not evaluable for toxicity because only one drug administration was given. Eighteen patients received a total of 67 courses through four dose levels. The dose-limiting toxicities were neutropenia and thrombocytopenia at the dose of 1.5 mg m-2 day-1. Nadirs occurred on day 15 and day 15 respectively. Other toxicities were mild and infrequent and included nausea/vomiting, headache and alopecia. The maximal tolerated dose was 1.2 mg m-2 day-1. One partial response was observed in a patient with colorectal cancer. The total plasma clearance was 999+/-184 ml min-1 (range 640-1329). The volume of distribution was 190+/-461 m-2 and the terminal half-life was 3.7+/-1.2 h. The AUC increased linearly with the administered dose. A steep and significant sigmoid relationship was established between the AUC and the percent decrease of ANC. GI147211 is a new topoisomerase I inhibitor that induced dose-limiting neutropenia and thrombocytopenia in this phase I study. The recommended dose for phase II studies with this schedule is 1.2 mg m-2 x 5 every 3 weeks.

Adult↗
PubMed1996

Phase II study of a short course of weekly high-dose cisplatin combined with long-term oral etoposide in metastatic colorectal cancer.

In a phase I study of weekly administered cisplatin combined with oral etoposide, we observed a partial response in 4 out of 11 patients with metastatic colorectal cancer. Subsequently, we performed a phase II study to investigate the activity of this combination as first-line treatment in this disease. Fourteen patients with metastatic colorectal cancer were enrolled in this study. Treatment consisted of cisplatin, administered in 3% sodium chloride, at a dose of 70 mg m-2 on days 1, 8 and 15 and days 29, 36 and 43 combined with oral etoposide 50 mg absolute dose daily on days 1-15 of both courses. Patients with stable disease or better continued treatment with etoposide 50 mg m-2 orally on days 1-21 every 28 days. A partial response was observed in two patients with liver metastases (14%; 95% confidence limits 2-42%) for 30 and 32 weeks. Five patients had stable disease. Toxicity consisted mainly of anaemia, leucocytopenia, nausea and vomiting. Tinnitus was reported by six patients. The activity of the combination cisplatin-oral etoposide in the schedule is only minimal in metastatic colorectal cancer.

Administration, Oral↗
PubMed1996

Bioavailability and pharmacokinetics of oral topotecan: a new topoisomerase I inhibitor.

The results of preclinical and clinical studies indicate enhanced antineoplastic activity of topotecan (SKF 104864-A) when administered as a chronic treatment. We determined the apparent bioavailability and pharmacokinetics of topotecan administered orally to 12 patients with solid tumours in a two-part crossover study. The oral dose of 1.5 mg m-2 was administered as a drinking solution of 200 ml on day 1. The i.v. dose of 1.5 mg m-2 was administered as a 30 min continuous infusion on day 2. The bioavailability was calculated as the ratio of the oral to i.v. area under the curve (AUC) calculated up to the last measured time point. The oral drinking solution was well tolerated. The bioavailability revealed moderate inter-patient variation and was 30% +/- 7.7% (range 21-45%). The time to maximum plasma concentration after oral administration (Tmax) was 0.78 h (median; range 0.33-2.5). Total i.v. plasma clearance of topotecan was 824 +/- 154 ml min-1 (range 535-1068 ml min(-1)). The AUC ratio of topotecan and the lactone ring-opened hydrolysis product (hydroxy acid) was of the same order after oral (0.34-1.13) and i.v. (0.47-0.98) administration. The bioavailability of topotecan after oral administration illustrates significant systemic exposure to the drug which may enable chronic oral treatment.

Administration, Oral↗
PubMed1996

Relationship between the exposure to cisplatin, DNA-adduct formation in leucocytes and tumour response in patients with solid tumours.

The study was designed to investigate possible relationships between tumour response and exposure to cisplatin (area under the curve of unbound cisplatin in plasma, AUC) and DNA-adduct formation in leucocytes (WBC) in patients with solid tumours. Patients were treated with six weekly courses of cisplatin at a dose of 70 or 80 mg m-2. The AUC was determined during the first course and DNA-adduct levels in WBC during all courses at baseline, 1 h (A(max)) and 15 h after a 3 h infusion of cisplatin. The area under the DNA-adduct-time curve (AUA) was calculated. The tumour response was determined after six courses. Forty-five evaluable patients received 237 courses of cisplatin. Sixteen patients with head and neck cancer received a dose of 80 mg m-2 and 29 with various other tumour types received 70 mg m-2 plus daily 50 mg oral etoposide. There were 20 responders (partial and complete) and 25 non-responders (stable and progressive disease). The AUC was highly variable (mean +/- s.d. = 2.48 +/- 0.51 micrograms h-1 ml-1; range 1.10-3.82) and was closely correlated with the AUA (r = 0.78, P < 0.0001) and A(max) (r = 0.73, P < 0.0001). The AUC, AUA and A(max) were significantly higher in responders than in non-responders in the total population (P < 0.0001) and in the two subgroups treated at 70 or 80 mg m-2. In logistic regression analysis AUC, AUA and A(max) were important predictors of response. The magnitude of exposure to cisplatin is, through DNA-adduct formation, the major determinant of the response rate in this population. Hence, individualised dosing of cisplatin using AUC or DNA-adducts should lead to increased response rates.

Adult↗
PubMed1996

Pharmacokinetic profile and clinical efficacy of a once-daily ondansetron suppository in cyclophosphamide-induced emesis: a double blind comparative study with ondansetron tablets.

We investigated the pharmacokinetic profile and the efficacy of ondansetron (day 1) given as 16 mg suppository once a day, as compared with ondansetron 8 mg tablets twice daily, in patients receiving moderately emetogenic chemotherapy. The study was primarily aimed at investigating the pharmacokinetics and was part of a large multinational, randomised, double-blind, double-dummy efficacy trial. Pharmacokinetic data were obtained in a total of 20 patients, 11 of whom had received a suppository containing ondansetron, and nine patients had received the oral formulation. The median area under the plasma concentration curve (AUC) obtained with the oral formulation was 226 ng ml-1h-1 (range 91-750), and the median maximum plasma level (Cmax) was 50.5 ng ml-1 (range 24.7-199.6) after a dose of 8 mg. For the ondansetron suppository the median AUC was 140 ng ml-1h-1 range (77-405) and the median Cmax was 17.1 ng ml-1 (range 13-48.3) after a dose of 16 mg. The systemic exposure after correction for the dose difference after the suppository was on average 70% lower than after the tablet. The median time to reach the maximum level (Tmax) was 60 min (range 28-120) with the oral formulation and 209 min (range 90-420) with the suppository. For both the tablet and suppository, there was no apparent relationship between either Cmax or AUC, and efficacy. Although the patient numbers were too small for a formal exposure-response relationship to be derived, the slightly poorer pharmacokinetic performance of the suppository did not appear to be associated with a lessening of control of emesis following chemotherapy. The study demonstrates that the pharmacokinetic analysis of a once-daily 16 mg ondansetron suppository results in appropriate plasma concentrations and AUC, and that this rectal formulation is effective in the protection against nausea and vomiting associated with cyclophosphamide chemotherapy. This formulation will provide a useful alternative to the currently available oral formulation.

Administration, Oral↗
PubMed1996

Multicentre phase II pharmacological evaluation of rhizoxin. Eortc early clinical studies (ECSG)/pharmacology and molecular mechanisms (PAMM) groups.

Rhizoxin is a macrocyclic lactone compound that binds to tubulin and inhibits microtubule assembly. Rhizoxin demonstrated preclinical anti-tumour activity against a variety of human tumour cell lines and xenograft models. Phase I evaluation found a maximum tolerated rhizoxin dose of 2.6 mg m-2, with reversible, but dose-limiting, mucositis, leucopenia and diarrhoea. Clinical trials were then initiated by the EORTC ECSG in melanoma, breast, head and neck, and non-small-cell lung cancers with the recommended phase II rhizoxin dose of 2 mg m-2. Pharmacological studies were instituted with the phase II trials to complement the limited pharmacokinetic data available from the phase I trial. Blood samples were obtained from 69 of 103 eligible patients enrolled in phase II rhizoxin studies, and these were evaluable for pharmacokinetic analysis in 36 patients. Plasma rhizoxin concentrations were determined by high-performance liquid chromatography (HPLC), and post-distribution pharmacokinetic parameters were estimated by a one-compartment model. Rhizoxin was rapidly eliminated from plasma, with a median systemic clearance of 8.41 min-1 m-2 and an elimination half-life of 10.4 min. Rhizoxin area under the concentration-time curve (AUC) was higher in patients obtaining a partial response or stable disease than in those with progressive disease (median 314 vs 222 ng ml-1 min; P = 0.03). As predicted from previous studies, haematological and gastrointestinal toxicity was observed, but could not be shown to be related to rhizoxin AUC. This study demonstrated the rapid and variable elimination of rhizoxin from the systemic circulation. The presence of pharmacodynamic relationships and the low level of systemic toxicity suggest that future trials of rhizoxin with alternative dosage or treatment schedules are warranted.

Antibiotics, Antineoplastic↗
PubMed1996

Interleukin 2 and interferon alpha-2a do not improve anti-tumour activity of 5-fluorouracil in advanced colorectal cancer.

Treatment using a combination of 5-fluorouracil (5-FU), interferon-alpha (IFN alpha-2a) and interleukin 2 (IL-2) has been shown to mediate disease regression in selected patients with advanced colorectal cancer. This phase II study was designed to evaluate the anti-tumour activity and toxicity of the combination of IL-2, IFN alpha-2a and 5-FU in patients with advanced colorectal cancer. Forty-four patients with metastatic colorectal cancer were treated, predominantly on an outpatient basis, with subcutaneous IFN alpha-2a and IL-2 three times per week followed by once a week bolus intravenous 5-FU injections. There were six (14%) partial responses among the 43 evaluable patients [95% confidence interval (CI) 5-28%]. Twenty-four patients had stable disease (56%) and 13 patients (30%) showed progressive disease. The median time to progressive disease in 43 patients was 19 weeks (range 2-72 weeks) and in responders 34 weeks (range 24-30 weeks). The median overall survival was 47 weeks (range 2-85 weeks) and in responders 60 weeks (range 35-71 weeks). Treatment-related toxic effects included fatigue, nausea and vomiting. Granulocytopenia was the main reason for the dose reductions or treatment interruptions in 32 out of 44 patients. One patient died of toxicity due to renal failure. Serial assessments of immunophenotyping and cytolytic activities of peripheral blood lymphocytes did not show changes in the numbers of circulating natural killer (NK) cells or in the levels of NK and lymphokine-activated killer (LAK) cytolytic activities. This regimen of IL-2 and IFN alpha-2a with 5-FU has only modest anti-tumour activity in advanced colorectal cancer.

Adenocarcinoma↗
PubMed1996

Phase II clinical trials with rhizoxin in breast cancer and melanoma. The EORTC Early Clinical Trials Group.

Rhizoxin is a new anti-tumour agent isolated from the pathogenic fungus Rhizopus chinensis. It has shown broad activity against murine tumour models and is also active against vinca alkaloid-resistant cells. The purpose of our studies was to determine the clinical activity of this compound in patients with advanced breast cancer and melanoma. Based on the results of a phase I study, 2.0 mg m-2 was administered as intravenous infusion over 5 min every 21 days. Nineteen patients were entered into the breast cancer phase II trial and received a total of 50 courses (median 2, range 1-6). Of these, dose reductions were performed in three courses because of leucopenia or stomatitis (1.5 mg m-2, one course; 1.45 mg m-2, two courses). Twenty-six patients were entered into the melanoma trial and received a total of 70 courses (median 2, range 1-12). No dose reductions were required. All patients were eligible for toxicity. Haematological toxicity included neutropenia CTC grade 3 (29/120 courses, 24.2%) and grade 4 (11/20 courses, 9.2%). Only drug-related CTC grade 1 thrombocytopenia was observed. Non-haematological toxicity included alopecia in all patients after two courses of treatment as well as CTC grade 3/4 stomatitis and asthenia. In the breast cancer study, one patient achieved a more than 50% tumour reduction after six cycles but was progressing after 6 weeks. Another patient showed a partial remission after the first course but was taken off the study because of CTC grade 3 skin toxicity. One patient was not evaluable for response (early death). No objective remissions were observed in 15 evaluable patients. In melanoma, no objective remissions were observed. We conclude that rhizoxin can be safely administered at 2.0 mg m-2 every 3 weeks. However, it has little activity in patients with advanced breast cancer and melanoma.

Adult↗
PubMed1996

Phase II study of rhizoxin in squamous cell head and neck cancer. The EORTC Early Clinical Trials Group.

To test the anti-tumour activity of rhizoxin in recurrent and/or metastatic squamous cell head and neck cancer, we performed a phase II study. Eligibility required histologically proven squamous cell head and neck cancer. Patients could only have received one prior chemotherapy. Patients were entered if WHO PS was < or = 2 and organ functions were normal. Treatment consisted of rhizoxin 1.5-2.0 mg m-2 i.v. bolus injection once every 3 weeks. Thirty-two patients entered the study. All were eligible, 31 were evaluable for toxicity and 25 for response. Toxicity mainly consisted of pain at the tumour site and leucocytopenia. Mild asthenia and stomatitis were also observed. Two objective partial responses, lasting 7.5 and 3.5 months, were seen. Rhizoxin at this dose and schedule has minor activity in recurrent and/or metastatic squamous cell head and neck cancer.

Adult↗
PubMed1996

Single agent activity of rhizoxin in non-small-cell lung cancer: a phase II trial of the EORTC Early Clinical Trials Group.

In a multicentre trial of the EORTC-Early Clinical Trials Group (ECTG) we treated 31 chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) with rhizoxin, a novel tubulin-binding agent. The drug was given as an i.v. bolus injection at 2 mg m-2 once every 3 weeks in an outpatient setting. Prophylactic antiemetics were not routinely given. Of the 29 eligible patients, nine had been treated surgically and three had received radiotherapy. The main toxic effects observed were stomatitis (34% of cycles) and neutropenia (41% of cycles). Neutropenic fever was rare (3% of cycles). Twenty-seven patients were evaluable for response. There were four partial responses (15%), while 13 patients (48%) showed stabilisation of their disease. The median duration of response was 7 months (range 6.0-10.7 months) and median survival from the start of rhizoxin treatment was 6 months (range 2-14.7 months). Rhizoxin as single agent shows activity in patients with advanced NSCLC.

Adult↗
PubMed1996

Phase II study of a closely spaced ifosfamide--cisplatin schedule with the addition of G-CSF in advanced non-small-cell lung cancer and malignant melanoma.

BACKGROUND: Ifosfamide and cisplatin are frequently combined cytotoxic agents. Both have a dose-response relationship. In view of this it appears attractive to study regimens with a higher dose intensity than usual. One way to increase the dose intensity is to shorten intervals between chemotherapy cycles. As bone marrow toxicity is dose limiting in ifosfamide-cisplatin combinations we started a phase II study with both drugs administered every 2 weeks in combination with G-CSF. PATIENTS AND METHODS: Patients with advanced non-small-cell lung cancer or malignant melanoma were eligible for the study. The treatment consisted of ifosfamide 2 gram/m2/day days 1-3 combined with mesna, and cisplatin 33 mg/m2/day days 1-3, administered in hypertonic saline (3% NaCl). G-CSF was started on day 4 at a dose of 5 micrograms/kg/day and was continued until day 12. The cycles were to be repeated every 2 weeks for a maximum of 6 cycles. RESULTS: Thirty-two patients were entered in the study; 30 patients were evaluable for response and toxicity. Neutropenia (grade 4 in 16 patients) and thrombocytopenia (grade 4 in 15 patients) were the most common toxicities. Thrombocytopenia incidence and -duration increased per cycle and was the main cause of treatment delays especially after the third cycle. Only 4 patients were able to complete the planned treatment without any delay or dose reduction and reached the intended dose intensity of 3 gram/m2/week of ifosfamide and 50 mg/m2/week of cisplatin. Non haematologic toxicities were generally mild. Out of 22 evaluable patients with non-small cell lung cancer 6 responded (27%; 95% CI: 10%-48%) while only one out of 8 patients with melanoma responded. The median response duration was 26 weeks (range 16-36 weeks). CONCLUSION: The planned high-dose intensity of ifosfamide and cisplatin could be reached only for the first 2-3 cycles. Haematologic toxicity, especially cumulative thrombocytopenia, necessitated treatment delays jeopardizing the dose intensity. The response rate in non-small-cell lung cancer and melanoma was not superior to what can be expected from more conventional regimens.

Adult↗
PubMed1996

Optimum anti-emetic therapy for cisplatin induced emesis over repeat courses: ondansetron plus dexamethasone compared with metoclopramide, dexamethasone plus lorazepam.

BACKGROUND: This study was undertaken to compare the efficacy and tolerability of ondansetron plus dexamethasone (O + D) with metoclopramide plus dexamethasone plus lorazepam (M + D + L) over three consecutive courses of cisplatin chemotherapy. PATIENTS AND METHODS: This was an international, multicentre, double-blind, double-dummy, parallel group study. O+D patients were randomised to receive ondansetron 8 mg intravenously (i.v.) plus dexamethasone 20 mg i.v. prior to cisplatin (50-100 mg/m2) chemotherapy. On the following 4 days they were treated with ondansetron 8 mg bd orally and dexamethasone 4 mg bd orally. M + D + L patients were randomised to receive metoclopramide 3 mg/kg i.v., dexamethasone 20 mg i.v. and lorazepam 1.5 mg/m2 i.v. (max 3 mg) prior to cisplatin chemotherapy and a further dose of metoclopramide 3 mg/kg i.v. approximately 2 hours following the first dose of metoclopramide. Treatment for the following 4 days was metoclopramide 40 mg tds and dexamethasone 4 mg bd orally. Two hundred and thirty-seven patients were recruited into the study (117 patients received O + D and 120 received M + D + L). RESULTS: On the first course chemotherapy, O + D was significantly superior to the M + D + L regimen for complete control of emesis (days 1-5, 54% versus 37%, respectively, P = 0.014). This was maintained over the three treatment cycles; 38% of O + D and 20% of M + D + L patients remained free of emesis (P = 0.003). Maintenance of control of nausea grade as none or mild on days 1-5 over the three courses was significantly better in the O + D group (48%) than in the M + D + L (26%, P = 0.003). The most commonly occurring adverse events in the O + D group were constipation (25%) and headache (19%). In the M + D + L group drowsiness (38% of patients), malaise/fatigue (16% of patients), constipation (13% of patients), anxiety (11% of patients) and dizziness (10% of patients) were the most commonly reported adverse events. Extrapyramidal symptoms were reported by 20% of patients in the M + D + L group. Despite the inclusion of lorazepam, 14% of patients in the M + D + L group were withdrawn from the study due to extrapyramidal symptoms, which in the opinion of the investigators, were probably or almost certainly related to study medication. CONCLUSION: This study show that O + D is significantly more effective and better tolerated than M + D + L for the control of emesis and nausea over a series of three courses of cisplatin chemotherapy.

Adult↗
PubMed1996

A randomized phase II study with two schedules of the novel indoloquinone EO9 in non-small-cell lung cancer: a study of the EORTC Early Clinical Studies Group (ECSG).

In a multicentre randomized trial of the EORTC-ECSG, we have treated 38 chemotherapy naïve patients with advanced non-small-cell lung cancer (NSCLC) with EO9, a novel bio-reductive alkylating indoloquinone. The drug was given at two different dose schedules by a single bolus i.v. injection: arm A 12 mg/m2 weekly and arm B 22 mg/m2 every three weeks. All together 185 courses were administered (145 in arm A and 40 in arm B). The major toxicity was reversible proteinuria more frequently occurring in the three-weekly schedule (arm A 34.5% vs. arm B 62.5%). Creatinine elevation, fluid retention and pericardial or pleural effusion were also recorded in a limited number of patients. Other common toxicities more frequent in the three-weekly administration were asthenia (21% vs. 35% of cycles), nausea (15% vs. 27.5% of cycles) and vomiting (5% vs. 17.5% of cycles). Toxicities were mainly of grade I and II. No responses have been observed. Five patients (26%) on arm A and eight (53%) on arm B experienced stable disease. These doses and schedules of EO9 do not yield activity in NSCLC.

Adult↗
PubMed1996

Phase II study on mitoxantrone in adenoid cystic carcinomas of the head and neck. EORTC Head and Neck Cancer Cooperative Group.

BACKGROUND: Based on activity in a case report, mitoxantrone was studied in a phase II study in adenoid cystic carcinoma. PATIENTS AND METHODS: Patients with symptomatic and/or rapidly progressive metastatic or recurrent adenoid cystic carcinoma were eligible for this study. They were treated with mitoxantrone given intravenously by bolus injection at a dose of 14 mg/m2, cycles repeated every 3 weeks. RESULTS: Thirty-six chemotherapy-naive patients entered on trial, 4 were ineligible. A median of 6 cycles per patient were given. Leucocytopenia (in 97% of patients) was the most important side effect and tended to be cumulative. Other side effects were mainly mild to moderate and consisted of nausea (62%), vomiting (29%), alopecia (53%) and mucositis (41%). Four of 32 patients had a partial response (12%; 95% CI 4%-29%) lasting 3-13 months, 22 patients (69%) had a stable disease. CONCLUSION: Mitoxantrone at this dose and schedule has modest activity in adenoid cystic carcinomas.

Adult↗