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I Judson

Publications and source records attributed to I Judson.

At least 37 records · Page 2Linked to original sources
PubMed2003

Molecular classification of synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas by gene expression profiling.

In this study, we have used genome-wide expression profiling to categorise synovial sarcomas, leiomyosarcomas and malignant fibrous histiocytomas (MFHs). Following hierarchical clustering analysis of the expression data, the best match between tumour clusters and conventional diagnosis was observed for synovial sarcomas. Eight of nine synovial sarcomas examined formed a cluster that was characterised by higher expression of a set of 48 genes. In contrast, sarcomas conventionally classified as leiomyosarcomas and MFHs did not match the clusters defined by hierarchical clustering analysis. One major cluster contained a mixture of both leiomyosarcomas and MFHs and was defined by the lower expression of a set of 202 genes. A cluster containing a subgroup of MFHs was also detected. These results may have implications for the classification of soft tissue sarcomas, and are consistent with the view that sarcomas conventionally defined as MFHs do not represent a separate diagnostic category.

Cluster Analysis↗
PubMed2003

Advanced soft-tissue sarcoma: a disease that is potentially curable for a subset of patients treated with chemotherapy.

Adult patients with metastatic or locally advanced irresectable soft-tissue sarcoma (ASTS) are generally considered as incurable. Whether some of these patients achieve long-term survival after first-line treatment with chemotherapy is not known. Patients with ASTS still alive 5 years after initial treatment with a doxorubicin-containing regimen, i.e. long-term survivors, were analysed among the 2187 patients included in first-line chemotherapy protocols between 1976 and 1990 in seven trials of the European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group (EORTC STBSG) group. 1888 patients were followed for at least 5 years. The initial clinical characteristics and the outcome of the long-term survivors were investigated. 66 of the 1888 patients were alive at 5 years and the projected 5-year survival was 8% in this series. Age or histological subtypes were similar in the long-term survivors compared with the other patients. The percentages of females (69%), of grade 1 tumours (35%), of patients with an initial performance status (PS) of 0 (63%) were significantly higher in the long-term survivors while liver metastasis (6% versus 21%) were significantly less frequent. Long-term survivors were observed in all subgroups of patients. 31, 31, 31 and 6% of the long-term survivors were in complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD), respectively, after the first-line regimen. A CR to a doxorubicin-containing regimen was the major parameter correlated to 5-year survival. In multivariate analysis using a logistic model, independent parameters correlated to 5-year survival were PS, female gender, grade I tumours, and the achievement of a CR after first-line treatment, which was retained as the most powerful predictor for 5-year survival. 10 of the 66 patients died after 5 years in this series, including 8 patients in PD or SD after first-line treatment versus 2 patients in PR or CR (P=0.01). 8% of patients with ASTS are alive 5 years after first-line chemotherapy with a doxorubicin-containing regimen. Long-term survivors are observed in all prognostic subgroups of patients, in particular those achieving a CR to first-line chemotherapy.

Adult↗
PubMed2003

Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study.

The aim of this study was to assess the antitumour response and time to progression (TTP) of patients treated with imatinib mesylate (Glivec, Gleevec, formerly STI-571) who had advanced and/or metastatic gastrointestinal stroma tumours (GIST) or other soft tissue sarcomas (STS). Patients with measurable lesions and adequate organ function were entered. They were treated with imatinib mesylate at the dose of 400 mg twice daily (bid). All tumours were subject to a stringent pathological review by an expert panel. Immunohistochemical expression of KIT expression was evaluated. A total of 51 patients (27 GIST, 24 other STS), median age 53 years, median World Health Organization (WHO) performance score 1, were entered. 71% of the patients had received prior chemotherapy. The most frequent side-effects were anaemia (92%), periorbital oedema (84%), skin rash (69%), fatigue (76%), nausea (57%), granulocytopenia (47%) and diarrhoea (47%). Most of these side-effects were mild to moderate and no patient was taken off study due to side-effects. Skin rash and periorbital oedema frequently seem to be self limiting, despite continued treatment. In GIST patients, the current response rates (RRs) are 4% complete remission (CR), 67% partial remission (PR), 18% stable disease (SD) and 11% progression (PD). 73% of GIST patients are free from progression at 1 year. In the other STS group, there were no objective responses. The median time to progression in this subgroup was only 58 days. Imatinib mesylate is well tolerated at a dose of 400 mg bid. This dose is active in patients with KIT-positive GIST, but patients with other STS subtypes unselected for a molecular target are unlikely to benefit.

Adult↗
PubMed2002

A study of amsalog (CI-921) administered orally on a 5-day schedule, with bioavailability and pharmacokinetically guided dose escalation.

PURPOSE: Amsalog is a derivative of 9-aminoacridine. Phase I studies using intravenous (i.v.) amsalog have shown the dose-limiting toxicity (DLT) to be phlebitis and myelosuppression. Phase II studies using a variety of schedules have shown evidence of activity in patients with large-cell lung, breast, and head and neck cancers. Preclinical studies demonstrated that amsalog is active orally: a clinical study of the oral bioavailability of amsalog was therefore performed. METHODS: A group of 20 patients with refractory malignancies were treated. There were two phases of the study: a pharmacokinetic comparison of i.v. against oral amsalog, followed by a pharmacokinetically guided oral dose escalation study. In the first phase of the study, 11 patients were treated. Amsalog 50 mg/m2 was administered i.v., and 50 mg/m2 and 200 mg/m2 orally. In the second phase of the study, 9 patients were treated in three cohorts of three. On day 1 of a 5-day schedule, amsalog was administered i.v. at the maximum tolerated dose (MTD) of 200 mg/m2. Subsequent doses were given orally, starting at a dose of 200 mg/m2 per day, with intrapatient dose escalation of up to 100% for the second cycle. Doses were escalated further in subsequent cohorts, based on oral bioavailability and toxicity. RESULTS: Oral bioavailability of 50 mg/m2 amsalog was 34%. In the dose escalation phase, DLT was neutropenia; other toxicities included malaise and nausea. The MTD was 1600 mg/m2 per day for 5 days. The plasma AUC using 1600 mg/m2 by the oral route was higher than that achieved using 200 mg/m2 by the i.v. route. CONCLUSION: Amsalog can be tolerated orally on a 5-day schedule at doses up to 1600 mg/m2. The recommended dose for further evaluation is 800 mg/m2 daily for 5 days, repeated three weekly.

Administration, Oral↗
PubMed2002

Progression-free rate as the principal end-point for phase II trials in soft-tissue sarcomas.

We have estimated progression-free rates (PFR) for various groups of soft-tissue sarcoma patients from our clinical trials database, to provide reference values for conducting phase II studies with PFR as the principal end-point. In 146 pretreated patients receiving an active agent, the PFR estimates were 39 and 14% at 3 and 6 months; with inactive regimens (234 patients), those estimates were 21 and 8% respectively. In 1154-non-pretreated patients, PFR estimates varied from 77% (synovial sarcoma) to 57% (malignant fibrous histiocytoma (MFH)) at 3 months, and from 56% (synovial sarcoma) to 38% (MFH) at 6 months. In 61 leiomyosarcomas from gastrointestinal origin, the corresponding figures were 44 and 30%, respectively. Consequently, for first-line therapy, a 6-month PFR of > or = 30-56% (depending on histology) can be considered as a reference value to suggest drug activity; for second-line therapy, a 3-month PFR of > or = 40% would suggest a drug activity, and < or = 20% would suggest inactivity.

Adolescent↗
PubMed2002

Results of randomised studies of the EORTC Soft Tissue and Bone Sarcoma Group (STBSG) with two different ifosfamide regimens in first- and second-line chemotherapy in advanced soft tissue sarcoma patients.

The aim of this phase II study was to evaluate the efficacy and toxicity of two regimens of ifosfamide in metastatic soft tissue sarcoma patients given as first- and second-line chemotherapy. Two different schedules of ifosfamide were investigated in a randomised manner: Ifosfamide was given either at a dose of 5 g/m(2) over 24 h (5 g/m(2)/1 day), every 3 weeks or at a dose of 3 g/m(2) per day, administered over 4 h on three consecutive days (3 g/m(2)/3 days), every 3 weeks. Both schedules were given as first-line or second-line chemotherapy. A total of 182 patients was entered, 103 in first- and 79 in second-line, of whom 8 patients were ineligible, 5 in the first- and 3 in the second-line study. Most patients had a leiomyosarcoma, 46 of the 98 in the first-line and 34 of the 76 in the second-line. The two study arms were well balanced in both the first- and second-lines with respect to sex, age and performance status. In first-line treatment, 5 g/m(2)/1 day yielded five partial responses (PR) (Response Rate (RR) 10%), versus 12 PR (RR 25%) for the 3 g/m(2)/3 days. As second-line treatment, the 24-h infusion yielded: one CR and one PR (RR 6%) and the 3-day schedule one CR and two PR (RR 8%). Survival did not differ between the two regimens. The major World Health Organization (WHO) grade 3 and 4 toxicities encountered were: leucopenia in 19% of all courses in the first-line and 32% in the second-line with the 5 g/m(2)/1 day, while for the 3 g/m(2)/3 days schedule the rates were 57 and 63% respectively. Grade 3 or 4 infections were seen in 4% of patients treated with 5 g/m(2)/1 day first-line and 10% of patients given 3 g/m(2)/3 days, both as first- and second-lines. No such infections were seen in patients receiving 5 g/m(2)/1 day as second line treatment. In advanced soft-tissue sarcomas in the first-line, ifosfamide 3 g/m(2), given over 4 h on three consecutive days, is an active regimen with acceptable toxicity while the 5 g/m(2) over 24 hours schedule resulted in a disappointing response rate.

Adult↗
PubMed2001

Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study.

BACKGROUND: Gastrointestinal stromal tumours (GISTs) are rare tumours of the gastrointestinal tract characterised by cell-surface expression of the tyrosine kinase KIT (CD117). No effective systemic treatment is available. Imatinib (STI571) inhibits a similar tyrosine kinase, BCR-ABL, leading to responses in chronic myeloid leukaemia, and has also been shown to inhibit KIT. We did a phase I study to identify the dose-limiting toxic effects of imatinib in patients with advanced soft tissue sarcomas including GISTs. METHODS: 40 patients (of whom 36 had GISTs) received imatinib at doses of 400 mg once daily, 300 mg twice daily, 400 mg twice daily, or 500 mg twice daily. Toxic effects and haematological, biochemical, and radiological measurements were assessed during 8 weeks of follow-up. 18Fluorodeoxy-glucose positron-emission tomography (PET) was used for response assessment in one centre. FINDINGS: Five patients on 500 mg imatinib twice daily had dose-limiting toxic effects (severe nausea, vomiting, oedema, or rash). Inhibition of tumour growth was seen in all but four patients with GISTs, resulting in 19 confirmed partial responses and six as yet unconfirmed partial responses or more than 20% regressions. 24 of 27 clinically symptomatic patients showed improvement, and 29 of 36 were still on treatment after more than 9 months. PET scan responses predicted subsequent computed tomography responses. INTERPRETATION: Imatinib at a dose of 400 mg twice daily is well tolerated during the first 8 weeks, side-effects diminish with continuing treatment, and it has significant activity in patients with advanced GISTs. Our results provide evidence of a role for KIT in GISTs, and show the potential for the development of anticancer drugs based on specific molecular abnormalities present in cancers.

Adult↗
PubMed2001

Randomised phase II trial of pegylated liposomal doxorubicin (DOXIL/CAELYX) versus doxorubicin in the treatment of advanced or metastatic soft tissue sarcoma: a study by the EORTC Soft Tissue and Bone Sarcoma Group.

CAELYX/DOXIL, pegylated liposomal doxorubicin, has shown antitumour activity and reduced toxicity compared with standard doxorubicin in other tumour types. In this prospective randomised trial, 94 eligible patients with advanced soft-tissue sarcoma (STS) were treated, 50 with CAELYX (50 mg/m(2) by a 1 h intravenous (i.v.) infusion every 4 weeks) and 44 with doxorubicin (75 mg/m(2) by an i.v. bolus every 3 weeks). Histological subtypes were evenly matched, 33% were leiomyosarcoma (CAELYX: 18; doxorubicin: 13). Primary disease sites were well matched. CAELYX was significantly less myelosuppressive, only 3 (6%) patients had grade 3 and 4 neutropenia, versus 33 (77%) on doxorubicin; febrile neutropenia occurred in 7 (16%) patients given doxorubicin, but only 1 (2%) given CAELYX. 37 (86%) patients on doxorubicin had grade 2-3 alopecia, but only 3 (6%) on CAELYX, and the major toxicity with CAELYX was to the skin. Palmar-plantar erythrodysesthesia with CAELYX was grade 1: 4 (8%) patients, grade 2: 11 (22%) patients, grade 3: 9 (18%) patients and grade 4: 1 (2%) patient. Other non-haematological grade 3 and 4 toxicities were rare. Confirmed responses were observed with both agents: CAELYX: complete response (CR) 1 (uterine), partial response (PR) 4 (response rate (RR) 10%); and doxorubicin: CR 1, PR 3 (RR of 9%); with the best response being stable disease (NC) in 16 and 18 patients, respectively. The reason for the low response rate is unknown, but it may be due partly to a high proportion of gastrointestinal stromal tumours. In conclusion, CAELYX has equivalent activity to doxorubicin in STS with an improved toxicity profile and should be considered for further investigation in combination with other agents such as ifosfamide.

Adult↗
PubMed2001

Cardiac metastasis from a myxoid liposarcoma.

Intracardiac metastases due to solid tumours are rare. We describe a patient with a myxoid liposarcoma of the thigh and a secondary lesion in the interventricular septum, which was treated with radiotherapy.

Antineoplastic Agents↗
PubMed2000

Phase I trial of 6-hour infusion of glufosfamide, a new alkylating agent with potentially enhanced selectivity for tumors that overexpress transmembrane glucose transporters: a study of the European Organization for Research and Treatment of Cancer Early Clinical Studies Group.

PURPOSE: To determine the maximum-tolerated dose (MTD), the principal toxicities, and the pharmacokinetics of 6-hour infusion of glufosfamide (beta-D-glucosylisophosphoramide mustard; D-19575), a novel alkylating agent with the potential to target the glucose transporter system. PATIENTS AND METHODS: Twenty-one patients (10 women and 11 men; median age, 56 years) with refractory solid tumors were treated with doses ranging from 800 to 6,000 mg/m(2). Glufosfamide was administered every 3 weeks as a two-step (fast/slow) intravenous infusion over a 6-hour period. All patients underwent pharmacokinetic sampling at the first course. RESULTS: The MTD was 6,000 mg/m(2). At this dose, two of six patients developed a reversible, dose-limiting renal tubular acidosis and a slight increase in serum creatinine the week after the second and third courses of treatment, respectively, whereas three of six patients experienced short-lived grade 4 neutropenia/leukopenia. Other side effects were generally mild. Pharmacokinetics indicated linearity of area under the time-versus-concentration curve against dose over the dose range studied and a short elimination half-life. There was clear evidence of antitumor activity, with a long-lasting complete response of an advanced pancreatic adenocarcinoma and minor tumor shrinkage of two refractory colon carcinomas and one heavily pretreated breast cancer. CONCLUSION: The principal toxicity of 6-hour infusion of glufosfamide is reversible renal tubular acidosis, the MTD is 6,000 mg/m(2), and the recommended phase II dose is 4, 500 mg/m(2). Close monitoring of serum potassium and creatinine levels is suggested for patients receiving glufosfamide for early detection of possible renal toxicity. Evidence of antitumor activity in resistant carcinomas warrants further clinical exploration of glufosfamide in phase II studies.

Adult↗
PubMed2000

Gene expression profiling of human colon cancer cells following inhibition of signal transduction by 17-allylamino-17-demethoxygeldanamycin, an inhibitor of the hsp90 molecular chaperone.

A number of molecular therapeutic agents, derived from exploiting our knowledge of the oncogenic pathways that are frequently deregulated in cancer, are now entering clinical trials. One of these is the novel agent 17-allylamino-17-demethoxygeldanamycin that acts to inhibit the hsp90 molecular chaperone. Treatment of four human colon cancer cell lines with iso-effective concentrations of this agent resulted in depletion of c-raf-1 and akt and inhibition of signal transduction. We have used gene expression array analysis to identify genes responsive to treatment with this drug. The expression of hsp90 client protein genes was not affected, but hsc hsp70, hsp90beta, keratin 8, keratin 18 and caveolin-1 were deregulated following treatment. These observations were consistent with inhibition of signal transduction and suggested a possible mechanism of resistance or recovery from 17-allylamino-17-demethoxygeldanamycin treatment. The results shed light on the molecular mode of action of the hsp90 inhibitors, and suggest possible molecular markers of drug action for use in hypothesis testing clinical trials. Oncogene (2000) 19, 4125 - 4133

Antibiotics, Antineoplastic↗
PubMed2000

Effect of high-dose ifosfamide in advanced soft tissue sarcomas. A multicentre phase II study of the EORTC Soft Tissue and Bone Sarcoma Group.

In this phase II study the effect of high-dose ifosfamide (HDI) given as a 3-day continuous infusion at a dose of 12 g/m2 repeated every 4 weeks with adequate mesna protection and hydration was evaluated in patients with advanced soft tissue sarcomas. A total of 124 patients entered the trial of which 10 were ineligible. HDI was given both as first-line and second-line chemotherapy. Median age was 46 years (19-66 years). Median World Health Organization (WHO) performance status was 1 (0-1). Fifty two per cent of the patients were males. The predominant histology was leiomyosarcoma (33%). A maximum of six cycles was given. At the time of analysis 55 patients have died. The partial response (PR) rate was 16%. The median time to progression was 15 weeks. 8 of the 18 responding patients (44%) had synovial sarcomas, whereas only 5% of the patients having leiomyosarcomas responded. The grade 3 + 4 haematological toxicity encountered was neutrophils in 78% and platelets in 12%. The major grade 3 + 4 non-haematological toxicities encountered were febrile neutropenia in 39%, infection in 20%, and acute renal failure in 4%. In conclusion, it is possible to administer HDI on a multicentre basis, but the toxicity is substantial. HDI given as a continuous infusion at this dose cannot be recommended as the standard treatment of advanced soft tissue sarcomas, even in selected patients.

Adult↗
PubMed2000

Randomized phase III study comparing conventional-dose doxorubicin plus ifosfamide versus high-dose doxorubicin plus ifosfamide plus recombinant human granulocyte-macrophage colony-stimulating factor in advanced soft tissue sarcomas: A trial of the European Organization for Research and Treatment of Cancer/Soft Tissue and Bone Sarcoma Group.

PURPOSE: This randomized multicenter study was designed to compare the activity of a high-dose doxorubicin-containing chemotherapy regimen with a conventional standard-dose regimen in adult patients with advanced soft tissue sarcomas (ASTS). PATIENTS AND METHODS: Between 1992 and 1995, 314 patients were randomized to receive a standard-dose regimen (arm A), containing doxorubicin (50 mg/m(2) on day 1) and ifosfamide (5 g/m(2) on day 1), or an intensified regimen (arm B), combining doxorubicin (75 mg/m(2) on day 1), the same ifosfamide dose, and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF; sargramostim, 250 microgram/m(2) on days 3 to 16); all courses were repeated every 3 weeks. RESULTS: The median age of the 294 eligible patients was 50 years. They received a median of five chemotherapy cycles. The median dose and relative doxorubicin dose-intensity achieved were 245 mg and 97% in arm A and 360 mg and 99% in arm B, respectively. Thirty-eight percent and 23% of patients presented with leiomyosarcomas and liver metastases, respectively. Objective responses were observed in 31 (21%) of 147 assessable patients in arm A and in 31 (23.3%) of 133 in arm B (P =.65). No change was observed in 41.6% and 46.2% of patients in arm A and B, respectively. Progression-free survival (PFS) was significantly longer in the intensive arm (P =.03). The median duration of the time to progression was 19 weeks in the conventional arm and 29 weeks in the intensified arm. There was no difference in overall survival (P =.98) between the two therapeutic arms. Toxicities were manageable in both arms. A grade 3/4 neutropenia and infection occurred in 92% and 4.6% of patients in arm A, respectively, and in 90% and 16.6% in arm B, respectively. Grade 3/4 thrombocytopenia was more frequent in arm B. CONCLUSION: The use of rhGM-CSF allowed safe escalation of chemotherapy doses. Despite a 50% increase of the doxorubicin dose-intensity, the high-dose regimen failed to demonstrate any impact on survival in patients with ASTS. The low complete response rate, the high incidence of leiomyosarcomas, and liver metastases may in part explain these results. However, the lengthening of the PFS in the intensive arm, because of the quality of stable disease and inappropriate tumor evaluation policies that potentially lead to an underestimation of antitumor activity, does not definitively refute the use of a high-dose chemotherapy regimen in selected patients with ASTS.

Adult↗
PubMed2000

New developments and approaches in the platinum arena.

Following the introduction of cisplatin and the demonstration of its importance in the treatment of testicular and ovarian cancer, there was a need to develop less toxic analogues. Compared with cisplatin, carboplatin proved markedly less toxic to the kidneys and nervous system and caused less nausea and vomiting, while generally (and certainly for ovarian cancer) retaining equivalent antitumour activity. In many situations, carboplatin is now the drug of choice in view of the improved quality of life it offers patients. Many drug combinations involving platinum complexes have been explored, but those with taxanes are particularly noteworthy. Paclitaxel in combination with a platinum agent is now accepted as a standard component of first-line treatment for ovarian cancer, and produces improved survival. Preclinical studies suggested that drugs containing the diaminocyclohexane ligand would be capable of overcoming intrinsic or acquired resistance. However, this outcome was not realised in the clinic until the development of oxaliplatin, which appears to have a different spectrum of activity compared with cisplatin and carboplatin. Oxaliplatin improves the response rate and progression-free survival when given with fluorouracil for the treatment of advanced colorectal cancer, and its activity in other tumour types is under investigation. ZD0473 is a platinum analogue that relies on steric hindrance to overcome thiol-mediated detoxification. It has a good tolerability profile, is currently undergoing phase II testing, and its activity in combination with other agents is being explored. The trinuclear platinum complex BBR3464 also looks promising in preclinical studies and will shortly be evaluated in phase II trials. Although much research remains to be done, these new developments in platinum-based chemotherapy should translate into significant improvements in treatment for patients with a broad range of tumour types.

Animals↗
PubMed1999

Effect of gastric pH on the relative oral bioavailability and pharmacokinetics of temozolomide.

PURPOSE: Temozolomide is an imidazotetrazine alkylating agent which undergoes chemical conversion at physiological pH to the active species 5-(3-methyltriazene-1-yl)imidazole-4-carboxamide (MTIC) but is stable at acid pH. This study evaluated the effect of an increase in gastric pH, through the use of ranitidine, on the oral bioavailability and plasma pharmacokinetics of temozolomide and MTIC. METHODS: Fifteen patients with advanced cancer were enrolled of which 12 were evaluable, all of whom had pharmacokinetic blood sampling. Each patient received temozolomide 150 mg m(-2) day(-1) for 5 days in cycle 1 and also received ranitidine 150 mg every 12 h either on days 1 and 2 or days 4 and 5. Gastric pH was monitored by the use of the Heidelberg capsule system. RESULTS: Following the administration of ranitidine there was a rise in gastric pH by 1-2 pH units over the duration of the study period (pH range 2.2-5.2 without ranitidine and 3.5-6.0 with ranitidine). There was no difference in the pharmacokinetic parameters of temozolomide or MTIC with or without the concomitant administration of ranitidine. There was however, a lower C(max) for temozolomide and MTIC for patients receiving ranitidine on day 1 and 2 versus day 4 and 5. Temozolomide was rapidly absorbed [time to maximum plasma concentration (t(max)) 1.8 h] and eliminated [elimination half-life (t(1/2)) 1.8 h] and MTIC followed a similar pattern with a t(max) of 1.9 h and a t(1/2) of 1.9 h. Overall, the AUC of the MTIC represented about 2-4% of the AUC for temozolomide.

Administration, Oral↗
PubMed1999

Temozolomide in adult patients with advanced soft tissue sarcoma: a phase II study of the EORTC Soft Tissue and Bone Sarcoma Group.

Temozolomide, an oral imidazotetrazine derivative, was given to 31 patients with advanced soft tissue sarcoma. The dose of 750 mg/m2 was divided over 5 consecutive days, and escalated to 1000 mg/m2 over 5 days at cycle 2 if myelosuppression no worse than common toxicity criteria grade 2 was noted in the first 28-day cycle. A total of 99 treatment cycles were given to 31 patients. The drug was well tolerated, with nausea and vomiting as the most common side-effects. Only one partial tumour response was documented, giving a response rate of 3.33%, 95% confidence interval, (CI) 0.1-17.2%. The median time to progression was 8 weeks and the median survival was 27 weeks. These results indicate that temozolomide in this schedule is not active as second-line treatment in advanced soft tissue sarcoma.

Adult↗