Sequential versus alternating chemotherapy for high-grade non-Hodgkin's lymphomas: preliminary results of a phase III multicentre trial

In a multicentre phase III trial 105 previously untreated patients with high-grade non-Hodgkin's lymphomas stage II-IV were randomized to receive either 4 cycles of CHOEP (cyclophosphamide 750 mg/m2 i.v. day 1, doxorubicin 50 mg/m2 i.v. day 1, vincristine 2 mg i.v. day 1, etoposide 100 mg/m2 i.v. days 3-5, prednisolone 100 mg p.o. days 1-5) (treatment arm A), or 4 cycles of chemotherapy with hCHOP (cyclophosphamide 1,200 mg/m2 i.v. day 1, doxorubicin 40 mg/m2 i.v. days 1 + 2, vincristine 2 mg i.v. day 1, prednisolone 100 mg p.o. days 1-5) alternating with IVEP (ifosfamide 1,500 mg/m2 i.v. days 1-5, vindesine 3 mg/m2 i.v. day 1, etoposide 120 mg/m2 i.v. days 3-5, prednisolone 100 mg p.o. days 1-5) in treatment arm B. After 4 cycles of chemotherapy an involved field irradiation with a total dose of 35 Gy was given to all patients demonstrated to be in complete or partial remission without persisting extranodal disease. A complete response (CR) was seen in 86/105 patients (82%) with 88% CR in arm A vs. 76% CR in arm B. During a median follow-up of 11 months (range 2-31 months) 13 patients relapsed (6 patients arm A, 7 patients arm B). The overall survival at 30 months is projected to be 72% vs. 83% for arm A and B respectively. Disease-free survival is projected to be 78% in arm A and 45% in arm B at 28 months. So far, the differences in CR, survival and disease-free survival are not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)     

Salvage chemotherapy for metastatic breast cancer: results of a phase II study with bendamustine.

BACKGROUND: Bendamustine, a bifunctional alkylating agent with anticipated purin-like properties is active in metastatic breast cancer (MBC) patients. This multicenter phase II trial defines the toxicity and activity of bendamustine in heavily pretreated patients. PATIENTS AND METHODS: Fifty-one patients were included. Patients had a median number of 2 prior chemotherapeutic regimens for MBC (range 0-7) consisting of anthracyclines and taxanes: 26 patients (51%); anthracyclines: nine patients (17.6%); taxanes: seven patients (13.7%); others: five patients (9.8%). Bendamustine was administered four weekly at a dose of 120 mg/m(2) on days 1 and 2. RESULTS: Fifty patients were assessable. Of total, 200 courses were administered. We observed no complete response (CR); 10 patients [20%; 95% confidence interval (CI): 10.0% to 33.7%] achieved a partial response (PR), 14 patients (28%) remained stable for at least 6 months resulting in a clinical benefit rate (CR + PR + stable disease) of 48% (95% CI: 33.7%to 52.6%). Median time to progression was 3.4 months (range 1-51.1). The median duration of remission was 6.6 months (range 1.8-48.7). The treatment was well tolerated with mainly hematologic toxic effects. CONCLUSION: Single-agent bendamustine is an active treatment in patients with MBC independent of the previous treatment. The low toxicity profile favors its use as a single agent.     

A phase II trial of primary temozolomide in patients with grade III oligodendroglial brain tumors

Glial tumors with oligodendroglial components are considered chemo-responsive. Forty newly diagnosed patients (11 anaplastic oligodendrogliomas [OD] and 29 anaplastic oligoastrocytomas [OA]) were enrolled into this multicenter, open-label, single-arm Phase II trial of first-line temozolomide (200 mg/m² on days 1–5 every 4 weeks for 6 cycles). The primary endpoint was 6-month progression-free survival (PFS) with response rate (RR), median PFS, and median overall survival (OS) as secondary endpoints. Of 39 evaluable patients at the 6-month time point (median follow-up, 34 months), 6-month PFS was 77% (95% confidence interval [CI], 74.5%–79.3%). There were 15 complete responses (CRs, 38%), 6 partial responses (PRs, 15%), and 9 disease stabilization (23%). The median PFS was 21 months (95% CI, 3–39 months), and the median OS was 43 months (95% CI, 20–66 months). Chromosome 1p/19q codeletions were seen in 47% (18 of 38) of the patients, and O-6-methylguanine-DNA-methyltransferase (MGMT) methylation was seen in 48% (10 of 21) of the patients. All patients with OD showed MGMT methylation and most (71%) had chromosome 1p/19q codeletions. Conversely, fewer patients with OA showed MGMT methylation (23%) or had chromosome 1p/19q codeletions (31%). The presence of either 1p/19q codeletion or MGMT methylation was associated with increased RR at 6 months but not with improved PFS or OS. Only 18% of the patients (7 of 40) experienced treatment-related grade 3/4 toxicities. This regimen was active and well tolerated. These data add to the growing body of data showing that primary chemotherapy may be an acceptable alternative to radiotherapy for patients with gliomas containing oligodendroglial histology.     

Liver complications in lymphomas treated with a combination of chemotherapy and radiotherapy: preliminary results

From May 1978 to May 1981, a total of 20 patients (18 patients with Non Hodgkin Lymphomas + 2 patients with Stage IV Hodgkin's disease) were treated with chemotherapy and whole or upper abdominal radiotherapy. All the patients were in complete remission at the time of irradiation. Shielding of the kidneys was effected at the start of treatment and the right lobe of the liver was shielded after a dose of 20 Gy was delivered. As of January 1982, 17 of the patients were alive and free of disease with a follow-up ranging from 6 to 32 months (mean follow-up of 18.5 months). Two patients were dead from their disease. Alterations in liver chemistry were observed in 5 patients, clinical jaundice or transient hepatomegaly along with changes in liver chemistry in 4 patients, classical veno-occlusive disease in 2 patients and 7 of the patients did not develop any complication. No death from complications were observed. The contribution of the following factors such as radiotherapy dose to the liver, drugs, nutritional status and associated medical conditions, towards the development of complications have been analyzed in detail.     

Salvage chemotherapy in anthracycline-pretreated metastatic breast cancer patients with docetaxel and gemcitabine: A multicenter phase II trial

Purpose: The activity of the docetaxel–gemcitabine combination in women with disease progression after initial chemotherapy for metastatic breast cancer (MBC) was investigated in a multicenter phase II study.Patients and methods: Fifty-two patients with metastatic breast cancer who had disease relapse or progression after completion of an anthracycline-based front-line regimen were treated with gemcitabine 900 mg/m2 on day 1 and day 8 and docetaxel 100 mg/m2 on day 8. G-CSF 150 µcg/m2/d s.c. was given from day 9 to day 16 and the treatment was repeated every three weeks. The patients' median age was 57 years and the performance status (WHO) was 0 for 26, 1 for 20 and 2 for 6 patients. The treatment was second-line for 27 (52%) and third-line for 25 (48%) patients. All patients were evaluable for response and toxicity.Results: Complete response occurred in seven (14%) patients and partial response in 21 (40%) for an overall response rate of 54% (95% confidence interval (95% CI): 40%–67%). Fifteen (29%) patients had stable disease and nine (17%) progressive disease. Of 25 patients previously treated with taxanes, 11 (44%) responded (1 CR, 10 PR). Interestingly, in four patients with disease progression while receiving docetaxel or paclitaxel monotherapy, the docetaxel + gemcitabine combination achieved partial responses. Responses were observed at all metastatic sites (local disease 62%, lymph nodes 58%, skin 44%, lung 47% and liver 36%) with a median duration of response of 3.6 months (range 1–16) and a median time to disease progression of eight months (range 2–18.5). Grade 3 neutropenia developed in 10 (19%) and grade 4 in five (10%) patients. Neutropenia was associated with infection in four patients without toxic deaths. Grade 3 thrombocytopenia developed in nine (17%) patients and grade 4 in two (4%). Non-hematologic toxicity was usually mild.Conclusion: The docetaxel–gemcitabine combination is an active and well tolerated salvage treatment in patients with MBC. Previous treatment with taxanes does not preclude a good clinical response to this regimen.     

Liposomal vincristine in relapsed non-Hodgkin's lymphomas: Early results of an ongoing phase II trial

Objective:Vincristine is an active agent in lymphomas, but isoften neurotoxic, and the resulting dose reductions have been associated withlower remission and survival rates in Hodgkin's disease. Liposomal vincristine(Onco-TCS) has prolonged half-life, reaches higher concentration in tumors andlymph nodes than in nerves, and administered at full doses appears to be lessneurotoxic, and more active then free vincristine in mice bearing L-1210 andP-388 leukemias. We therefore explored its activity in relapsed non-Hodgkin'slymphomas (NHL) and acute lymphoblastic leukemia (ALL). Patients and methods:Eligible patients had histologically provenrelapse, age 16 years, normal renal function, neutrophils>500/µl, platelets >50,000/µl, and no HIV infection, centralnervous system disease, or serious neuropathy. Patients were treated with 2.0mg/m² of liposomal vincristine i.v. over 60 minutes q 14 days.Responders received up to 12 injections. Results:Of the 51 registered patients, 35 are currently evaluablefor response. Median age was 62 years (range 19–86), and 21 were male.The median number of prior regimens was 3 (range 1–10) and had includedvincristine in all patients, of whom 51% were refractory to their lastregimen. Serum LDH was high in 46%, and 2–microglobulin >3.0mg/l in 63% of patients. Of the 155 administered injections, 138(89%) were at the 2.0 mg/m² level. The median injected dosewas 3.8 mg (range 2.6–4.8 mg), and median number of injections was 4(range 1–12). Responses were seen in 14 of 34 (41%) patients withNHL (95% confidence intervals (95% CI)25%–59%). Response rates were 10% for indolent,71% for transformed, and 47% for aggressive NHL, but the95% confidence intervals overlapped. Median progression-free survivalwas 5.5 months for responders. Grade 3–4 motor or sensory neuropathy wasseen in 11, and caused termination of therapy in five patients. All five hadprior neuropathy, two had previously received paclitaxel, one platinum, andtwo paclitaxel and platinum. Fever was detected in three patients, but therewere no toxic deaths. Conclusions:Liposomal vincristine is active and well toleratedin this heavily pretreated population with relapsed NHL, but can be neurotoxicin a fraction of patients heavily exposed to prior neurotoxic agents. Thesedata, if confirmed, would suggest a potential role for liposomal vincristinein the combination therapy of previously untreated patients with NHL.     

Induction chemotherapy of non-Hodgkin's malignant lymphomas: Preliminary results of a controlled trial

Thirty-three patients have been included in a randomized trial comparing cyclophosphamide + vincristine + prednisone (CVP) + VM 26 (CVPV) and CVP + adriamycine (CVPA). The tolerance is good for the two regimens. There is no difference between the two protocols, which clearly give better results than CVP alone.     

Temozolomide in non-small-cell lung cancer: preliminary results of a phase II trial in previously treated patients

Virtually all patients with advanced non-small-cell lung cancer (NSCLC) relapse. Docetaxel has an established, Food and Drug Administration-approved role as salvage therapy in previously treated, platinum-exposed patients. However, the response rate in phase III studies is < 15%, and median survival is only 6-8 months. Temozolomide, a novel triazene derivative with activity in melanoma and anaplastic astrocytoma, has demonstrated activity in C26 adenocarcinoma, Lewis lung cancer, and in phase I studies. A phase II trial was mounted using a unique schedule of oral temozolomide 75 mg/m2 daily for 6 weeks every 8-10 weeks, in patients with previously treated, advanced, incurable NSCLC. Eligibility stipulated an Eastern Cooperative Oncology Group performance status (PS) of 0-2, adequate end organ function, up to 1 prior chemotherapy for advanced (relapsed or metastatic) disease, and up to 1 prior regimen in the context of radiosensitization, adjuvant therapy, or induction. From March 2000 through January 2002, 47 patients (24 male, 23 female) were enrolled. The median age was 67 years. Sixteen patients had a PS of 2, 22 had a PS of 1, and 9 had a PS of 0. It was too early to evaluate 9 patients. Toxicity, with the exception of mild nausea and thrombocytopenia, was negligible. Three patients had a delayed recovery of platelets prompting discontinuation of treatment. Of the 38 evaluable patients, 1 patient had a complete response, 2 patients had a partial response, 12 had stable disease, and 19 had disease progression. Four patients were not evaluable. Six patients died within 30 days of taking temozolomide; 5 of these deaths were not related to treatment upon review by an independent data safety monitoring committee. Temozolomide, using a unique 6-week continuous schedule, has demonstrated activity in the salvage therapy of advanced NSCLC. Toxicity is modest, and accrual to this study continues.     

Hypofractionated radiation therapy versus chemotherapy with temozolomide in patients affected by RPA class V and VI glioblastoma: a randomized phase II trial

Journal of Neuro-Oncology - In RPA V-VI glioblastoma patients both hypofractionated radiotherapy and exclusive temozolomide can be used; the purpose of this trial is to compare these treatment...     

Phase II study of primary temozolomide chemotherapy in patients with WHO grade II gliomas.

BACKGROUND: The aim of this study was to assess the efficacy of temozolomide in patients with World Health Organisation (WHO) grade II gliomas treated with surgery alone using imaging and clinical criteria. PATIENTS AND METHODS: Thirty patients with histologically verified WHO grade II gliomas (17 astrocytoma, 11 oligodendroglioma, two mixed oligoastrocytoma) following surgery 2-104 months (median 23 months) after initial diagnosis received temozolomide 200 mg/m(2)/day for 5 days, on a 28-day cycle, for a maximum of 12 cycles or until tumour progression. Median age was 40 years (range 25-68 years). Median follow-up from entry into the study was 3 years [range 23-47 months (for patients alive)]. Objective response was assessed by 3-monthly magnetic resonance imaging and monthly health-related quality of life (HQoL) and clinical assessment. Tumour size was measured as the high signal intensity area on fluid attenuated inversion recovery sequences. Responses were assessed using change in the product of two perpendicular diameters as complete response (CR), partial response (PR), minimal response (MR), stable disease (SD) and progressive disease (PD). RESULTS: Twenty-nine of 30 patients entered into the study were evaluable for response. Three patients had a PR, 14 MR, 11 SD and one PD. Twenty-four patients received 12 cycles of chemotherapy. Of 29 evaluable patients, three discontinued after four, five and six cycles and two after 10 cycles. Nine patients progressed (three during chemotherapy-one PD and two initial SD-and six after completion of chemotherapy); five had evidence of transformation. The 3-year progression-free survival was 66%. Five patients died; the actuarial 3-year survival was 82%. Ninety-six per cent of patients with impaired HQoL had improvement in at least one HQoL domain. There was improvement in 115 of the 207 domains (56%). Fifteen of 28 patients (54%) with epilepsy had reduction in seizure frequency, of whom six became seizure free. Six patients had transient grade III/IV haematological toxicity (11 episodes; 3.5%). CONCLUSIONS: Temozolomide has single-agent activity in patients with WHO grade II cerebral glioma, with modest improvement in quality of life and improvement in epilepsy control. On present evidence, temozolomide cannot be considered as primary therapy without formal comparison with other treatment modalities.     

Gemcitabine and vinorelbine combination chemotherapy for patients with advanced soft tissue sarcomas: results of a phase II trial

BACKGROUND: Single-agent gemcitabine and vinorelbine have activity in treatment of patients with soft-tissue sarcomas. The combination of gemcitabine plus vinorelbine has activity against several forms of metastatic carcinoma with acceptable toxicity. This study evaluated the efficacy and tolerability of gemcitabine plus vinorelbine in advanced soft-tissue sarcoma. METHODS: A single academic center performed this phase II trial. Eligible patients had unresectable or metastatic soft-tissue sarcomas, Eastern Cooperative Group performance status of 0-2, adequate organ function, and 4 months. There has been 1 CR lasting >1 year in a patient with high-grade pleomorphic spindle-cell sarcoma. CONCLUSIONS: Gemcitabine given by a fixed-dose rate of infusion combined with vinorelbine was associated with clinically meaningful rates of disease control in patients with advanced soft-tissue sarcoma. Toxicity was acceptable. This study contributed to data that have supported the administration of fixed-dose rate gemcitabine-based drug regimens in soft-tissue sarcomas.     

Regional chemotherapy for unresectable primary liver cancer: results of a phase II clinical trial and assessment of DCE-MRI as a biomarker of survival

BackgroundThis study reports the results of hepatic arterial infusion (HAI) with floxuridine (FUDR) and dexamethasone (dex) in patients with unresectable intrahepatic cholangiocarcinoma (ICC) or hepatocellular carcinoma (HCC) and investigates dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) assessment of tumor vascularity as a biomarker of outcome.Patients and methodsThirty-four unresectable patients (26 ICC and eight HCC) were treated with HAI FUDR/dex. Radiologic dynamic and pharmacokinetic parameters related to tumor perfusion were analyzed and correlated with response and survival.ResultsPartial responses were seen in 16 patients (47.1%); time to progression and response duration were 7.4 and 11.9 months, respectively. Median follow-up and median survival were 35 and 29.5 months, respectively; 2-year survival was 67%. DCE-MRI data showed that patients with pretreatment integrated area under the concentration curve of gadolinium contrast over 180 s (AUC 180) >34.2 mM·s had a longer median survival than those with AUC 180 <34 mM·s (35.1 versus 19.1 months, P = 0.002). Decreased volume transfer exchange between the vascular space and extracellular extravascular space (-ΔK^trans) and the corresponding rate constant (-Δk_ep) on the first post-treatment scan both predicted survival.ConclusionsIn patients with unresectable primary liver cancer, HAI therapy can be effective and safe. Pretreatment and early post-treatment changes in tumor perfusion characteristics may predict treatment outcome.     

Salvage chemotherapy with mitomycin, docetaxel, and irinotecan (MDI regimen) in metastatic pancreatic adenocarcinoma: a phase I and II trial

BACKGROUND: This study evaluates the maximum tolerated dose (MTD) and activity of mitomycin, docetaxel, and irinotecan (MDI) regimen on metastatic pancreatic adenocarcinoma, previously treated with gemcitabine-containing chemotherapy. PATIENTS AND METHODS: Patients with less than 76 years, Karnofsky performance status > or = 60, and adequate bone marrow, kidney, and liver function were eligible for this trial. Treatment consisted of mitomycin 6 mg/m2 day 1, docetaxel and irinotecan on days 2 and 8 with escalating doses, every 4 weeks. Dose levels were level 1:30 and 70 mg/m2; level 2:30 and 100 mg/m2; level 3:30 and 85 mg/m2; and level 4:35 and 85 mg/m2. Dose-limiting toxicity (DLT) was defined as grade 4 neutropenia > 7 days, febrile neutropenia, grade 4 thrombocytopenia, nausea and vomiting, or diarrhea, grade > or = 3 nonhematological toxicity, or failure to recover to grade < or = 1 toxicity by day 43, occurring during the first cycle of chemotherapy. RESULTS: Between September 2001 and October 2002, 15 eligible patients, three of whom had been previously treated with two lines of chemotherapy, received 33 cycles of MDI. Toxicity consisted of grade 3 to 4 neutropenia in 23% of cycles, fatigue, diarrhea, and vomiting in 10% of cycles, and one toxic death. DLT was observed in 2 of 6 level 2 patients (one toxic death and one grade 3 fatigue), and 2 of 3 level 4 patients (one neutropenic fever and one grade 3 fatigue). Thirteen patients were assessable for response. No objective response was observed among patients treated with MTD or higher doses. Three patients had stable disease; all other patients had progressive disease. The median time to tumor progression and median survival was 1.7 and 6.1 months, respectively. CONCLUSION: The MTD was mitomycin 6 mg/m2 day one, and docetaxel 30 and irinotecan 85 mg/m2 days 2 and 8. This regimen is inactive in metastatic pancreatic cancer.     

Phase II trial of gemcitabine plus trastuzumab in metastatic breast cancer patients previously treated with chemotherapy: preliminary results

Preliminary results of a phase II study of gemcitabine plus trastuzumab in previously treated (up to 3 previous regimens) metastatic breast cancer patients are presented. Patients had histologically confirmed metastatic breast cancer, with 2+ or 3+ tumor HER2 expression. Treatment consisted of gemcitabine 1200 mg/m2 over 30 minutes intravenously on days 1 and 8 every 21 days, and trastuzumab 4 mg/kg over 90 minutes, followed by 2 mg/kg infused over 30 minutes weekly. Treatment was continued until disease progression or unacceptable toxicity occurred. Preliminary results are available on the first 38 patients enrolled. Median patient age was 53 years, 53% had estrogen receptor/progesterone receptor-positive disease, and HER2 staining was 2+ in 39% and 3+ in 61% of patients. There was a median of 3 previously administered (including adjuvant) chemotherapy regimens, and a median of 4.5 treatment cycles per patient has been administered so far. Twelve patients (32%) have had an objective partial response, with a median response duration of 8.6 months. Median time to disease progression is 6.7 months to date, with a median overall survival of 10.2 months. No unexpected toxicities or grade 4 nonhematologic toxicities have been observed; 2 patients developed grade 4 neutropenia and 1 patient had febrile neutropenia. Thus, gemcitabine/ trastuzumab resulted in an encouraging 32% response rate, given the heavily pretreated patient population. Tolerability was good overall, with no unexpected side effects observed.     

Early relapses in primary CNS lymphoma after response to polychemotherapy without intraventricular treatment: results of a phase II study

Background A systemic and intraventricular polychemotherapy regimen (the Bonn protocol) without radiotherapy resulted in durable responses in 75% of patients <60 years with primary CNS lymphoma (PCNSL), but was complicated by a high rate of Ommaya reservoir infections. Here, the efficacy and toxicity of this regimen without intraventricular treatment was evaluated in PCNSL. Patients and methods From August 2003 to November 2005, 18 patients with PCNSL <60 years (median age, 53 years) were treated in a phase II trial with a high-dose methotrexate (MTX; cycles 1, 2, 4 and 5) and cytarabine (Ara-C; cycles 3 and 6) based systemic therapy including dexamethasone, vinca-alkaloids, ifosfamide and cyclophosphamide. Results Study accrual was prematurely stopped in November 2005 due to a high rate of early relapses. Seventeen of 18 patients were assessable for response: nine (53%) achieved complete response (CR), two (12%) complete response/unconfirmed (CRu) and two (12%) partial response (PR); four (24%) showed progressive disease (PD). One treatment was stopped due to toxicity. Median follow-up was 23 months, median response duration was only 10 months in responding patients, and median time to treatment failure (TTF) was 8 months in the whole group. Median overall survival (OS) has not been reached. Systemic toxicity was mainly hematologic. Conclusions In PCNSL patients <60 years, polychemotherapy without intraventricular treatment results in a high response rate, but is associated with early relapses in the majority of cases. This is in contrast to the results achieved with the same protocol but with intraventricular treatment. H. Pels and A. Juergens contributed equally.     

Multicenter phase II trial of temozolomide in patients with glioblastoma multiforme at first relapse

Background:Recurrent glioblastoma multiforme (GBM) is resistantto most therapeutic endeavors, with low response rates and survival rarelyexceeding six months. There are no clearly established chemotherapeuticregimens and the aim of treatment is palliation with improvement in thequality of life. Patients and methods:We report an open-label, uncontrolled,multicenter phase II trial of temozolomide in 138 patients (intent-to-treat[ITT] population) with glioblastoma multiforme at first relapse and aKarnofsky performance status (KPS) 70. One hundred twenty-eight patientswere histologically confirmed with GBM or gliosarcoma (GS) by independentcentral review. Chemotherapy-naïve patients were treated withtemozolomide 200 mg/m²/day orally for the first five days ofa 28-day cycle. Patients previously treated with nitrosourea-containingadjuvant chemotherapy received 150 mg/m²/day for the first fivedays of a 28-day cycle. In the absence of grade 3 or 4 toxicity, patients onthe 150 mg/m² dose schedule were eligible for a 200mg/m² dose on the next cycle. Results:The primary endpoint was six-month progression-freesurvival assessed with strict radiological and clinical criteria. Secondaryendpoints included radiological response and Health-related Quality of Life(HQL). Progression-free survival at six months was 18% (95%confidence interval (CI): 11%–26%) for theeligible-histology population. Median progression-free survival and medianoverall survival were 2.1 months and 5.4 months, respectively. The six-monthsurvival rate was 46%. The objective response rate (complete responseand partial response) determined by independent central review ofgadolinium-enhanced magnetic resonance imaging (MRI) scans was 8% forboth the ITT and eligible-histology populations, with an additional 43%and 45% of patients, respectively, having stable disease (SD).Objectively assessed response and maintenance of a progression-free statuswere both associated with HQL benefits (characterized by improvements overbaseline in HQL domains). Temozolomide had an acceptable safety profile, withonly 9% of therapy cycles requiring a dose reduction due tothrombocytopenia. There was no evidence of cumulative hematologictoxicity. Conclusions:Temozolomide demonstrated modest clinical efficacy,with an acceptable safety profile and measurable improvement in quality oflife in patients with recurrent GBM. The use of this drug should be exploredfurther in an adjuvant setting and in combination with other agents.     

Immunohistochemical analysis of adhesion molecules and matrix metalloproteinases in malignant CNS lymphomas: a study comparing primary CNS malignant and CNS intravascular lymphomas

Two distinct forms of malignant lymphomas can invade the central nervous system (CNS). Although primary CNS malignant lymphomas (PCNSMLs) invade the brain parenchyma, intravascular lymphomas (IVLs) form tumor cell aggregates in the vasculature and produce stroke-like symptoms and cognitive impairment. Although the tumor cells are mostly of B-cell origin in both types of lymphoma, their biological behavior is different, and the detailed mechanism(s) underlying this difference are not well understood. We studied the expression level of the adhesion molecules intercellular adhesion molecule-1 (ICAM-1) and integrin-β1 in tumor tissue samples from patients with primary CNS lymphoma (n = 8) and intravascular lymphoma (n = 2) using immunohistochemical analysis. We also assessed the expression of the matrix metalloproteinases (MMP)-2 and MMP-9. ICAM-1 was positive in six and integrin-β1 was positive in seven patients among eight PCNSML patients. MMP-2 and MMP-9 were expressed in all PCNSML. In contrast, none of them was positive in both IVL cases. Our findings suggest that adhesion molecules and MMPs are essential for malignant lymphoma cell invasion from the vasculature into the brain parenchyma and that they may be the key determinants for malignant lymphoma cells to behave as PCNSML or IVL cells.