Lee R Morgan

• Dekk-Tec, Inc

Central nervous system (CNS) malignancies are rare, but commonly fatal and glioblastoma (GBM) is the most common of the primary brain tumors. In contrast to metastatic malignancies involving the CNS, which have external blood supplies that develop when the malignant cells penetrate the blood-brain-barrier (BBB), GBM generates its own intracerebral...

Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate that was designed to penetrate the blood brain barrier and be useful as therapy for brain tumors (IND 68,876). A 3-stage mechanism is proposed for drug entry into the CNS and into cancer cells via reversible binding with si...

Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N⁷-guanine and N⁴-cytosine that has completed Phase I and II trials (the latter including subjects with CNS involvement) [AACR #1185, 2013; AACR #CT 129, 2019]. The primary aims of the...

In 2020 about 89,000 adolescents and young adults (AYA) (ages 15 to 39) were estimated to be diagnosed with cancer in the United States, 23,890 had CNS and spinal nervous system(SNS) involvement—accounting for one twentieth or five percent of the number cancer diagnoses in the United States. The estimated deaths for this group was18,020 deaths in 2...

Purpose: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N⁷-guanine and N⁴-cytosine that has completed Phase I/II studies [AACR, #CT129, 2017] in adult subjects with cancers involving the CNS. Four (4) subjects in the Phase I/II trials required...

Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N7-guanine and N4-cytosine that has completed Phase I and now in Phase II clinical trials in AYA subjects with cancer with CNS involvement. The aims were to assess clinical responses,...

Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N⁷-guanine and N⁴-cytosine DM-CHOC-PEN has completed Phase I/II studies as a single agent and as a radiosensitizer in subjects with cancers involving the CNS [AACR #CT129, 2016; CT069,...

Purpose: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N⁷-guanine and N⁴-cytosine that has completed Phase II studies [AACR, #CT129, 2017] in subjects with cancers involving the CNS. Four (4) subjects in the Phase I/II trials required surgery...

Purpose: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N⁷-guanine and N⁴-cytosine that has completed Phase II studies [AACR, #CT129, 2017] in subjects with cancers involving the CNS. Four (4) subjects in the Phase I/II trials required surgery...

Purpose:4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a mechanism of action (MOA) via bis-alkylation of DNA @ N⁷-guanine and N⁴-cytosine that has completed Phase I/II studies [AACR, 58, #CT129, 2017] in subjects with cancers involving the CNS. Four (4) subjects in the Phase I...

4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine carbonate with a MOA via bis-alkylation of DNA @ N7-guanine and N4-cytosine that has completed adult clinical Phase I and II trials in individuals with malignancies involving the CNS. We report here objective clinical observations seen in a clinical Phase I...

Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N⁷-guanine and N⁴-cytosine that has completed phase I and II trials in adult subjects with cancer that had +/- CNS involvement (AACR #1185, 2013; AACR #CT 129, 2017). The aims were to...

Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA bis-alkylation of DNA @ N⁷-guanine and N⁴-cytosine that has completed Phase I and II trials (the latter on subjects with CNS involvement) [AACR #1185, 2013; AACR #CT 129]. The primary aim was to assess clinical r...

Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N⁷-guanine and N⁴-cytosine that has completed Phase I/II studies [AACR #CT129, 2016] in subjects with cancers involving the CNS. The current presentation reviews clinical and in vitro...

Background: 4-Hydropeoxyifosfamide (HOOI) is a hydroperoxy derivative of ifosfamide that was developed as an anticancer agent that can penetrate the blood-brain barrier (BBB), which can be potentially useful in the management of brain tumors. Methods: A novel synthetic scheme for HOOI is presented and verified. HOOI and an HOOI L-lysine salt were p...

Neurooncology anticancer drugs are no exception—their distribution and tissue interactions follow the general rules of classical pharmacology. In an attempt to assist with the new therapeutic approaches to manage cancers involving the central nervous system, classical chemobiodynamic compartment and pharmacokinetic models are discussed and illustra...

BACKGROUND DM-CHOC-PEN is a poly-chlorinated pyridine cholesteryl carbonate that has completed a Phase I/II study [AACR #1185, 2013; #CT129, 2016] in subjects with primary brain cancers and metastatic cancers involving the CNS. We review clinical and in vitro data that support radiosensitizing properties of DM-CHOC-PEN. PATIENTS AND METHODS DM-CHO...

PURPOSE DM-CHOC-PEN is a polychlorinated pyridine cholesteryl carbonate, which is in Phase I clinical trials in patients with advanced cancer. B-16 melanoma was evaluated in vitro and in vivo for sensitivity to DM-CHOC-PEN. METHODS B-16 melanoma cells were cultured and drugs were added to the cells in a growth phase and after 16 hrs removed. Adult...

Background: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate with a MOA via bis-alkylation of DNA @ N7-guanine and N4-cytosine that has completed a Phase I study [AACR #1185, 2013] and is being evaluated in a Phase II trial in patients with primary brain cancers and with melanoma, br...

Purpose: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate whose MOA is via bis-alkylation of DNA @ N7 - guanine and N6 - cytosine. DM-CHOC-PEN has undergone a Phase I study (allowed enrollment of subjects with advanced cancer +/- CNS involvement) and is being evaluated in a Phase II...

Background: The gold standard in treatment of high-grade astrocytomas includes resection, concomitant temozolomide (TMZ) and radiation followed by maintenance TMZ. The efficacy of TMZ is limited by drug-resistance mediated by O6-methylguanine-DNA methyltransferase (MGMT). Brain metastases are difficult to treat and currently no standard chemotherap...

INTRODUCTION: Pineal parenchymal tumors of intermediate differentiation (PPTID) represent less than 0.04% of brain tumors. Due to the rarity of this disease, there is no consensus as to appropriate treatment of this tumor. We present a patient with PPTID and our novel approach thereafter. CASE: A 34 year-old male presented with headache, nausea a...

DM-CHOC-PEN has undergone a Phase I study and is being evaluated in a Phase II trial in patients with primary brain cancer and brain metastases from melanoma, breast, and lung cancers. The aims are to assess clinical responses to IV DM-CHOC-PEN at maximum tolerated dose and to monitor toxicities, pharmacokinetics, and cardiac functions - IND 68,876...

Purpose: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN), is a poly-chlorinated pyridine cholesteryl carbonate whose MOA is via alkylation of DNA @ N7 - guanine and N6 - cytosine and via oxidative stress. DM-CHOC-PEN underwent a phase I study in patients with advanced cancer +/- CNS involvement and is being evaluated in a phase II tri...

The authors describe the case of a patient who initially presented with uterine leiomyosarcoma (LMS) that later metastasized to the spine. The patient was treated at another institution for her primary uterine LMS, undergoing resection followed by adjuvant chemotherapy. After several years of disease remission, the patient presented in January 2011...

Purpose: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate whose MOA is via alkylation of DNA @ N7 - guanine and via oxidative stress. The aims of this clinical trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs), pharmacokinetics (PK) and mon...

Introduction: DM-CHOC-PEN is a polychlorinated pyridine cholesteryl carbonate, which has completed a Phase I clinical trial in patients with advanced cancer - IND 68,876 (AACR 1185, 2013). DM-CHOC-PEN produced responses with improved cerebral progression free intervals (CPFI) in patients with CNS melanoma, breast, and lung cancers. CNS melanoma is...

Purpose: 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine cholesteryl carbonate whose MOA is via alkylation of DNA @ N7 - guanine and induces oxidative stress. The main aims of this first-in human trial were to determine maximum-tolerated dose (MTD), safety, dose-limiting toxicities (DLTs) and pharmacokin...

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC BACPTDP is a dipeptide prodrug of the 7-butyl-10-amino analog of camptothecin (BACPT) that is nearing clinical development. BACPTDP was selected based on its ability to exploit the tumor pH gradient that exists in tumors growing in hypoxic and acidic extracellular microenv...

The present disclosure concerns complexes of 4-hydroperoxy ifosfamide. In one embodiment the complexes can be represented by the formula wherein A represents an ammonium species selected from the conjugate acid of a basic amino acid, quaternary ammonium, aliphatic ammonium, heterocyclic ammonium, aromatic ammonium, substituted and unsubstituted py...

This study examined the relationship between Australian children's acceptance of self and their stage of friendship expectations. Subjects, 116 boys and 92 girls (8 to 13 years old), completed the Piers-Harris Children's Self-Concept Scale and a Picture Sequence Task. The results showed that children who were at the evaluation, admiration, and comm...

Proceedings: AACR 103rd Annual Meeting 2012‐‐ Mar 31‐Apr 4, 2012; Chicago, IL 4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a polychlorinated pyridine cholesteryl carbonate, which is active vs. intracranially (IC) implanted human xenograft models - U251 and D54 glioblastoma and MX-1 breast cancer (%LTS/CR): +29/25 and +20/17, re...

Introduction: 4-Demethyl-4-cholesteryloxycarbonyl-penclomedine (DM-CHOC-PEN) is a polychlorinated pyridine cholesteryl carbonate, which is in Phase I clinical trials in patients with advanced cancer - IND 68,876. DM-CHOC-PEN is active vs. intracranially (IC) implanted human xenograft models - U251 and D54 glioblastoma and MX-1 breast cancer and rec...

Proceedings: AACR 102nd Annual Meeting 2011‐‐ Apr 2‐6, 2011; Orlando, FL HOOI is a hydroperoxy-derivative of ifosfamide (IFOS) and a pro-drug of isophosphoramide mustard (IPM) [the active metabolite of IFOS] – a bi-functional alkylator that cross-links with G/C DNA base sequences resulting in irreparable inter-strand DNA cross-linking and cell dea...

Hypoxia is a common feature of solid tumors. Up-regulation of hypoxia-inducing factor-1 (HIF-1) occurs in the majority of primary malignant tumors and in two-thirds of metastases, while most normal tissues are negative. HIF-1 induces the glycolytic phenotype, which creates an acidic extracellular microenvironment and associated pH gradient such tha...

4,4′-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) formed stable double salts with phenothiazin-5-ium salts (2a–d), which have improved in vitro anticancer activities, as compared to A-007 alone. The stable salt between methylene blue (2a) and A-007 allowed the latter to diffuse into the dermis layers of skin. It is anticipated that thes...

This study examined the relationship between Australian children's acceptance of self and their stage of friendship expectations. Subjects, 116 boys and 92 girls (8 to 13 years old), completed the Piers-Harris Children's Self-Concept Scale and a Picture Sequence Task. The results showed that children who were at the evaluation, admiration, and comm...

s: AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics--Nov 15-19, 2009; Boston, MA Hypoxia is a common feature of solid tumors. Related up‐regulation of hypoxia‐inducing factor‐1 (HIF‐1) occurs in the majority of primary malignant tumors and in two‐thirds of metastases, while most normal tissues are negative. HIF‐1...

The purpose of this investigation was to synthesize a series of carbonate and carbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma non-toxic metabolite of penclomedine (PEN) seen in patients. DM-PEN has been observed to be an active antitumor agent in mouse human xenograft tumor models and non-neurotoxic in a rat model, howeve...

Introduction Most chemotherapy drugs (5‐FU, penclomedine (PEN), phosphamides) that alter memory are pyrimidines, pyridines or other pseudohetero‐cyclic rings that could interact with/antagonize the CNS N‐methyl‐D‐aspartate (NMDA)receptor complex ‐ a memory transmitter pathway. NMDA has numerous neurotransmitter substrates ‐ glutamate, serine, glyci...

Arylsulfatase B activity has been determined in 24-hour urine samples from 243 patients with colorectal cancer. Elevated activity of the enzyme was observed in 172 out of 243 (71%) patients. Employing Dukes' modified classification of colorectal cancer, urine arylsulfatase B activity was elevated in Dukes' A lesions—1/8 (12%), Dukes' B lesions—24/4...

This study is to document the activity and acceptability for a new topical agent, A-007, in the treatment of cutaneous metastases from cancer. This is a multicenter study involving 27 patients with inoperable skin lesions from histologically confirmed cancers of the breast and oral cavity, non-Hodgkin's lymphoma, Kaposi's sarcoma, and angiosarcoma...

9524 Background: IPM is a bi-functional alkylator which cross-links DNA through G:C base-pairs resulting in irreparable 7-atom inter-strand cross-links. IPM is the active moiety of ifosfamide (IFOS), a pro-drug of IPM. IPM is active in diverse cancer models but is unstable. We stabilized IPM with lysine (IPM-lysine; ZIO-201). ZIO-201 was active in...

Isophosphoramide mustard (IPM) is the cytotoxic alkylating metabolite of Ifosfamide (IFOS). IPM is being readied for a phase I clinical trial. In the present preclinical study, IPM was evaluated for usage in multidose intravenous (IV) infusion protocols. Mice and dogs received IV IPM daily for 3 days. Single-day dosing-oral and IV-to mice, rats, an...

Isophosphoramide mustard (IPM) is known to have substantial anti-cancer activities in various animal models. Liquid chromatography–electrospray mass spectrometry (LC–ES–MS) and LC–ES–MS/MS methodologies have been developed and applied to the analysis of synthesized preparations of IPM. Our studies reveal that the principal impurity in IPM is N-(2-c...

4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has recently completed a phase I clinical trial in advanced cancer with minimal toxicity, and impressive objective responses were noted. A-007 possesses three moieties that appear to have an influence on its anticancer activities: diphenylmethane, hydrazone, and dinitrophenyl. The goals...

The structure of the anticancer agent 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) has been modified through SAR and by incorporating barbituric acid, pyridine, quinoline, and alkylcarboxylic acids into A-007's moieties. Analogue anticancer activity and interacting with CD surface markers on a T-cell leukemia cell line were evaluat...

4,4'-Dihydroxybenzophenone-2,4-ditrophenylhydrazone (A-007) has demonstrated anticancer activities, when administered topically to patients with metastatic cancer to the skin. Acute, subacute and subchronic dermal studies with A-007 in adult rabbits, rats, guinea pigs and monkeys failed to demonstrate local or systemic toxicity when applied topical...

4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) formed stable double salts with phenothiazin-5-ium salts (2a-d), which have improved in vitro anticancer activities, as compared to A-007 alone. The stable salt between methylene blue (2a) and A-007 allowed the latter to diffuse into the dermis layers of skin. It is anticipated that thes...

The purpose of this investigation was to compare the antitumor activities of a series of acyl derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma metabolite of penclomedine (PEN) observed to be an active antitumor agent in vivo and non-neurotoxic in a rat model with that of DM-PEN. Acyl derivatives were prepared from DM-PEN and evaluat...

4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) is being evaluated for its anticancer activities. Acute, subacute and chronic oral, dermal, opthalmic and dermal LD50 and acceptance studies in adult mice, rats, rabbits and monkeys demonstrated some vomiting at 5 g/kg doses in monkeys but otherwise no unacceptable toxicities. In vitro,...

4,4'-Dihydroxybenzophenone-2,4-dinitrophenylhydrazone (A-007) is being evaluated for its anticancer activities in melanoma, breast cancer, Kaposi's sarcoma and lymphoproliferative disorders. A single oral dose of 1 g/kg of A-007 in rats resulted in prolonged and low plasma levels, typically less than 150 ng/ml for several days. Similarly, a single...

A new group of fluorescent organic materials having a variety of uses are described. They are especially useful as dye compounds in dye laser systems, and as photochemical agents in the treatment of diseased tissues using photodynamic therapy techniques.

An analytical method has been developed for the determination of 4,4'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (I, trade name A-007) in plasma. Plasma samples are primed with the internal standard, 2,2'-dihydroxybenzophenone-2,4-dinitrophenylhydrazone (II), deproteinized with acetonitrile, centrifuged and filtered prior to assay. The compon...

Thirty-six patients were entered on this study to determine the pharmacology, bioavailability, and toxicity of three different oral formulations of cyclophosphamide (Cytoxan, Endoxan, and an investigational direct compression tablet). Patients were randomized with respect to the order in which they received the different oral cyclophosphamide prepa...

Potassium fluoride on alumina catalysed the N-alkylation of aromatic and heteroaromatic 2,4-dinitrophenylhydrazones with alkyl and benzyl halides in the absence of solvent.

Patients with advanced renal cell carcinoma, previously failed maximal treatment with standard chemo-hormonal-radiation therapies, were treated with plant lectin phytohemagglutinin (PHA)-stimulated autologous peripheral blood lymphocytes in a 10-year study with a 16-year follow up period. In a phase I-II setting, 52 patients were given subcutaneous...

Quasiaromatic heterocycles (QAM) such as substituted 1 , 3 , 5 , 7 , 8-pentamethylpyrromethene boron difluorides (PMP-BF2) and - (dimethoxyphosphinylmethyl, methyl) bimane have been evaluated for their abilities to produce cellular toxicities when used in photodynamic therapy (PDT) for ovarian cancer. The most active QAH tested to date has been the...

An analytical method has been developed for the determination of N-acetylcysteine in human serum following acetaminophen overdosage in humans. Serum samples were treated with dithiothreitol and the protein-freed product was derivatized with 2,4-dinitrofluorobenzene. N-Acetylhomocysteine thiolactone was used as an internal standard. Following diethy...

Activated charcoal is a safe, effective, inexpensive adjunct in the management of most toxic ingestions. It has the ability to adsorb a wide variety of drugs and chemicals, one of which is acetaminophen. N-acetylcysteine (NAC) is the specific antidote available for serious overdoses of acetaminophen. Current management of acetaminophen overdose, ho...

One hundred six postmenopausal patients with advanced breast cancer received megestrol acetate or tamoxifen as primary therapy. Response to therapy was comparable for the two agents, with no organ site preference observed for either agent. The median duration of remission was also comparable for the two agents. Both treatments were well tolerated,...

In supporting the human-tumor cloning effort of the Southwest Oncology Group, we conducted an independent retrospective study to evaluate the clinical correlations of the soft-agar colony-forming assay developed by Hamburger and Salmon (1977). This study was made with the cooperation of 76 clinicians and 11 hospitals in Greater New Orleans. In a 10...

The influence of oxygen on the growth and the in vitro chemosensitivity of human tumor cells was studied in the soft-agar assay. Tumor cells of pancreatic and ovarian origin prefer a reduced oxygen atmosphere for colony formation, whereas those of pulmonary origin grow better in 20% oxygen. Depending on the physiologic oxygen tension and the histol...

The effects of racemic sodium warfarin (warfarin) and sodium heparin (heparin) on brain tumor cells were assessed in the rat C6 glioma cell line. After anticoagulant treatment lasting up to 5 days, cell growth was not inhibited by warfarin at low doses (10(-4) to 10(-5) M), but both cell growth and cellular adherence to culture plates were inhibite...

Soft-agar clonogenicity of L1210 mouse leukemia cells and of xenografts of a human melanoma and a carcinoma of the cervix was studied sectionally by the sizes of the colonies grown under hypoxic gradients and aerobic condition. Soft-agar plating efficiency was increased in cultured L1210 cells with decreasing oxygen concentrations. The growth of bo...

This study tested the feasibility of using oral ifosfamide to treat bronchogenic carcinoma and compared the pharmacokinetics of intravenous and oral doses of the drug. Patients with advanced bronchogenic carcinoma were evaluated for toxicities associated with oral ifosfamide therapy. Pharmacokinetics for various oral and intravenous doses of ifosfa...

Intravesical mitomycin C therapy was administered to 63 patients with noninvasive bladder carcinoma in a phase I-II study. Doses ranged from 20 to 60 mg once a week for 8 weeks. The overall response rate was 67% including a complete remission rate of 45%. The median duration of complete remission for the two lowest dose groups was > 14 months, with...

To see whether urine enzyme activities could be used as an index in evaluating the disease status of leukemia patients, we examined the activities of four enzymes: arylsulfatases A(AS-A) and B(AS-B), alkaline phosphatase (AP), and lactate dehydrogenase (LDH). AP and LDH showed no consistent patterns. The activities of AS-A and AS-B correlated well...

An overview of the pharmacology of drugs in the treatment of cancer is presented. The discussion begins with the simplest relationship of drugs and particles to one another then proceeds to demonstrate the interrelationship in a biologic system to produce a chemobiodynamic response. The basic principles of pharmacokinetics are reviewed and their co...

PGA1 and PGA2 significantly depressed melanoma cell DNA synthesis and cell proliferation in a dose related fashion. Inhibition of DNA synthesis was rapid in onset (0.5–1 hr) and sustained (12 hr). This was not due to general cytotoxicity or depression of substrate uptake. Comparison with known cancer chemotherapeutic agent revealed PGA1 and PGA2 ef...

An automated assay for arylsulfatase A activity has been developed because of its apparent clinical usefulness in the diagnosis of metachromatic leukodystrophy and as a prognostic indicator in malignant disease. The automated assay is based on the widely used method of Baum et al.

5-Flourouracil (5-FU) and methyl-CCNU have demonstrated separate sensitivities in carcinoma of the large bowel. This study was an attempt to see if methyl-CCNU versus methyl-CCNU plus 5-FU would demonstrate different responses in advanced colorectal carcinoma. Forty-nine patients have been evaluated, 14 receiving methyl-CCNU and 35 receiving 5-FU p...