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PubMed1982

[A case report of an aged patient with erythroleukemia coexistent with pulmonary emphysema, responding well to AAAP therapy].

A case of erythroleukemia coexistent with pulmonary emphysema is reported. A 67-year-old male was admitted to our hospital in May 1981, with a few year history of cough, sputum and fatigue. He had already been diagnosed as having pulmonary emphysema and moderate anemia. On physical examination, except for pallor, no other findings were remarkable. The initial hematological examination showed hemoglobin, 9.6 g/dl, red cell count, 251 x 10(4)/microliters, platelet count, 7.3 x 10(4)/microliters, white cell count, 2600/microliters with neither myeloblasts nor erythroblasts. A sternal marrow aspiration revealed 21% myeloblasts and 40% erythroblasts including 7.5% megaloblastoids. Periodic Acid Schiff staining was strongly positive for a part of erythroblasts. A chest X-P finding was typical for pulmonary emphysema. Pulmonary function was moderately damaged. He was started on chemotherapy with AAAP (ACNU 50 mg/d i.v. drip over 4 hr x 4d, adriamycin 20 mg/d i.v. push x 4d, Methotrexate 20 mg i.v. push x 4d). The first course of AAAP brought him a complete remission with both disappearance of myeloblasts and erythroid precursors with megaloblastoid nuclei in the marrow and the normalization of white cell count and platelet count in the blood. He was discharged in September 1981 after completion of a consolidation chemotherapy with AAAP. Since then, he received two courses of AAAP as an intensification chemotherapy and has been in complete remission for more than 13 months. His pulmonary function has not been affected and no myocardial damage has been seen throughout AAAP therapy. Thus, AAAP therapy seems to be an excellent chemotherapy even for an aged patient with erythroleukemia.

Aged↗
PubMed1982

[Evaluation of local administration of ACNU in the treatment of malignant pleural effusion].

Five patients with malignant pleural effusion were treated with intrapleural administration of ACNU. Three of 5 patients showed cytologically negative in the pleural fluid and the fluid was eliminated in two patients. In 5 patients, 200 mg of ACNU was injected into the pleural space and pharmacokinetic behavior was studied. The clearance curves of ACNU in pleural fluid were described by either one-compartment model or two-compartment model. The mean half life of slow phase was 0.75 hour. These results indicate that ACNU disappears rapidly from the pleural space after the intrapleural administration. The effect of ACNU on the pleura was studied histologically in rabbits. At a dose of 3mg per kg body weight, the mesothelial cells were swelling and small areas of cellular desquamation appeared over the pleural surface. With increase in dosage, these findings were more pronounced and in the submesothelial tissue there was edema as well as cellular infiltration. In rabbits given two injections with interval of one week, the pleura showed a stronger reaction than that produced by single injection.

Adult↗
PubMed1982

[Inhibitory effect of antineoplastic agents on human cholinesterases].

Human motor endplate acetylcholinesterase was inhibited in vitro by alkylating antineoplastic agents, most strongly by mechlorethamine, followed by DTIC, ACNU, cyclophosphamide and ifosfamide. Eleven other antineoplastic agents did not inhibit the enzyme substantially nor interfered with cholinesterase measurement. Cyclophosphamide and mechlorethamine inhibited human plasma pseudocholinesterase most strongly, followed by thiotepa, ACNU, DTIC, ifosfamide and BCNU. Mechlorethamine, ACNU and ifosfamide inhibited the motor endplate and plasma cholinesterase practically equally, DTIC inhibited motor endplate cholinesterase more strongly, while cyclophosphamide was a more selective inhibitor of plasma cholinesterase. Inhibition of human red blood cell acetylcholinesterase was identical to that of motor endplate acetylcholinesterase; therefore, red cells would be a preferable indicator in monitoring cholinesterase inhibition by antineoplastic agents.

Acetylcholinesterase↗
PubMed1982

[A combination chemotherapy of ACNU and DTIC for advanced malignant melanoma].

Fourteen patients with advanced malignant melanoma were treated with a combination chemotherapy consisting of ACNU 100 mg/m2 i.v. on Day 1 in 6 week intervals and DTIC 200 mg/m2 i.v. on Days 1 to 5 at 3 week intervals. Four patients had prior chemotherapy and 2 had prior immunotherapy. Excluding 4 patients received the regimen for adjuvant chemotherapy, 10 of 14 patients were evaluable for response. There were 3 patients of partial responses, 3 minor responses, 1 no change, and 3 progressive diseases. The durations of partial responses were 1, 1, and 8 months, respectively, while the survival times in these patients were 5, 21, and 10 months, respectively. Leukopenia less than 4,000/cmm occurred in 10 of 14 patients (71%) and thrombocytopenia less than 100 X 10(3)/cmm in 9 of 14 patients (64%), moreover, these hematologic toxicities were cumulative. Serum GOT and GPT elevated to 3,460 mu/ml and 1,365 mu/ml, respectively in one patient, but this returned to a normal level one month later. Nausea and vomiting were mild to severe in 12 of 14 patients, being most marked on Day 1 and decreasing intensity during the next several days. Other non-hematologic toxicities including skin rash, fever, and phlebitis were noted in each one patient, respectively. Hematologic toxicity of this regimen was a dose limiting toxicity; therefore, intensive supportive therapy to prevent infection and hemorrhage is essential for the management of the patients during this chemotherapy.

Adult↗
PubMed1982

[Two cases of central nervous system leukemia which responded excellently to intra-arterial injection of ACNU].

Local chemotherapy by intra-arterial administration of ACNU was performed in 2 cases with CNS leukemia, which responded well to this therapy. The first patient was a 42-year-old male who was diagnosed as having chronic myelogenous leukemia with local infiltration of leukemic cells to the optic nerves. By intra-arterial infusion of ACNU (60mg), symptoms and results of ophthalomological examinations were improved remarkably. The second case was a 16-year-old male diagnosed as having acute lymphoblastic leukemia, and complicating with meningeal involvement during the course of chemotherapy. Complete remission was achieved by intra-thecal administration ACNU. Intra-arterial infusion of ACNU would be an effective local chemotherapy of CNS leukemia and its effectiveness could be achieved by less dose of ACNU compared to that of intravenous infusion. Therefore, side effects, e.g., delayed myelosuppression caused by ACNU could be decreased by this method.

Adolescent↗
PubMed1982

[The combination chemotherapy of vincristine, methotrexate, ACNU, and adriamycin for anaplastic carcinoma of the lung].

Recent advances in the chemotherapy of malignant diseases, particularly, in hematopoietic malignancies, has opened oncologists' eyes in wonder, whereas the chemotherapy of solid malignant diseases including the carcinoma of the lung is not satisfactory compared with the results of other modalities such as radiotherapy and surgery. The chemotherapy, however, gradually becomes a great importance because the majority of the cases of lung cancer is that of advanced one. Between June, 1974 and December 1980 we experienced 54 inoperable cases of lung cancers among which there were 11 cases diagnosed as an anaplastic carcinoma. The combination chemotherapy of vincristine (1 mg/body, iv, day 1), methotrexate (30 mg/body, iv, day 1 and 5), ACNU (100mg/body, iv, day 2) and adriamycin (40mg/m2, iv, day 2) was employed. Vincristine and methotrexate were given every 3 weeks and ACNU and adriamycin were repeated every 9 weeks. If the moderate degree of neuropathy due to vincristine occurred it was suspended and methotrexate was stopped if WBC was less than 2000/mm or if patients were suffered from stomatitis which disturbed their swallowing. According to the response criteria of Koyama-Saito 4, cases were responded and one of them survived 17 months after the initiation of above 4-drug combination chemotherapy, although she received another combination chemotherapy because of the relapse of disease. The combination chemotherapy of ACNU and adriamycin was tried to utilize the advantage of their time different effects on the bone marrow suppression and to cover heterogenous histopathological diagnosis of anaplastic carcinoma. The heterogeneity of anaplastic carcinoma included undifferentiated squamous cell carcinoma, adenocarcinoma, large cell carcinoma and even small cell carcinoma. In taking consideration of these points, the drug-combination was designed. Clinically, however, the long resting period made the tumor regrow in some cases due to severe delayed myelosuppression by the combination of ACNU and adriamycin. Thus, more cautiously-designed combination should be considered.

Aged↗
PubMed1982

[Postoperative treatment of malignant brain tumors with ACNU and PSK-particularly immunological follow-up research].

From the recent progress in immunological study, many authors have reported immune suppression in patients with malignant brain tumors. On the other hand, many factors are considered to influence the patterns of cellular and humoral immune parameters in patients with brain tumors, pre- and post-operatively. We treated the patients with malignant brain tumors using ACNU and PSK pre- and post-operatively, and 4 year survival rate was 35.3% (N: 17) in glioblastomas. We planned this time to measure immune parameters (Ig,lymprocyte number,Lyn and T-cell, Tn) pre- and post-operatively in order to study the immune states of patients. The results were as follows: The most significant finding was the elevated serum level of IgG in longterm survival of the patients with glioblastoma and the reduced one in patients with postoperative death. No other humoral immunocompetence existed except slightly reduced IgM level in the patients with death. Contrary to many previous studies, our research has suggested that humoral immune parameters are considered to be valuable to understand postoperative immune states of patients, and administration of PSK be effective as an immunomodulator.

Adult↗
PubMed1982

[Topical application of ACNU for the treatment of mycosis fungoides].

The effects of topical chemotherapy of 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) on the lesions of mycosis fungoides were evaluated in 7 patients, ranging in age from 44 to 79 years old. Either 0.2% or 0.4% concentration of ACNU, in ointment and ethanol was used. 0.4% ACNU ethanol solution was effective in bringing the plaque lesions under satisfactory control with a complete clearance. ACNU was painted two to three times a week with a maximum dose of 50mg. Irritation and erosion of the applied areas were the major side effects, which were however, controlled by topical steroid ointment. No serious side effects of marrow and liver function were found even when ACNU was applied as long as 40 months (total ACNU dose: 16 gm). Histologically the cleared lesions revealed the thinning of epidermis, almost complete loss of lymphocytic infiltrates and fibrosis of dermis which was density infiltrated by lymphocytes prior to the ACNU therapy. Thus, topical chemotherapy of ACNU appears to be encouraged for modifying the plaque lesions of mycosis fungoides.

Administration, Topical↗
PubMed1982

[Pharmacokinetics of ACNU in cerebrospinal fluid].

Various nitrosoureas are widely used effectively for chemotherapy of brain tumors, clinically and experimentally. Fourteen cases of malignant brain tumor received intravenous injection of 100-150 mg/body of ACNU, and the concentration of ACNU in blood and cerebrospinal fluid (CSF) was measured. The conclusion drawn from this study on penetration of ACNU is summarized as follows: 1. ACNU concentration in CSF and its ratio to that of serum (CSF/serum %) showed the various values of 0-0.076 micrograms/ml (0-63%), 30 min. after administration; 2. Concentration of ACNU in spinal CSF differed from that in ventricular CSF and CSF/serum ratio was 19.9% in spinal CSF and 42% in ventricular CSF, respectively; 3. Statistically no correlation between ACNU CSF/serum ratio and the postoperative time was found. Transition of ACNU into cerebrospinal fluid during radiation therapy was noted with high value of CSF/serum ratio.

Adolescent↗
PubMed1982

[Malignant melanoma in Japan: unique distribution and effect of DAV chemoimmunotherapy].

This study, based on a co-operative group project involving 4 major medical institutes in Japan presents the first survey of malignant melanoma (MM) patients (157 cases) where an attempt was made to systemically evaluate the distribution of primary MM, and the response to DAV-chemoimmunotherapy. The distribution of primary MM in Japan is unique in a sense that the MM involving the lower extremities occupied more than 50% of the total male and female cases. The commonest type and site of involvement is the acrolentiginous MM involving the plantar area (30%). The regimen of our group included the combination of DTIC, VCR and ACNU, a new nitrosourea with or without immunoadjuvants OK-432, PSK, or NK-421). By a historical comparison, the DAV-treated group showed a better prognosis in the survival rates of overall (Stages I-IV) and disseminated (Stages III-IV) patients than those of the non-DAV group. However, the effect of combined immunoadjuvants was not statistically significant, though OK-432 showed a significant inhibition of lymphopenia which always occurred during DAV therapy.

Adjuvants, Immunologic↗
PubMed1994

[Effective measures against side effects by increasing ACNU dose for malignant glioma: effects on digestive organs].

Loading therapy consisting of the ACNU regimen was instituted as postoperative anticancer chemotherapy for malignant gliomas. The efficacy rate of the regimen was 25% at a dose of 3 mg/kg. A high incidence of hematological changes, such as leukopenia (neutropenia) and thrombocytopenia, were observed after chemotherapy. The former could be prevented by the administration of G-CSF, but platelet infusions were necessary in some patients for amelioration of thrombocytopenia. Gastroenterological symptoms, such as nausea and vomiting, were also frequently noted. Granisetron (Kytril), which is a recently developed selective competitive inhibitor of the 5-HT3 receptor, was used for the treatment of these adverse effects, and was found to be clinically effective.

Adult↗
PubMed1995

[Chemotherapy of malignant melanoma].

At present, the chemotherapeutic combinations for melanoma available are three regimens using DAV, PAV and CDV. Among of them, the DAV combination (dacarbazine, ACNU, vincristine) and PAV (peplomycin, ACNU, vincristine) are used as post-operative adjuvant therapy for stage II and III patients. Their aim is to prevent recurrence and prolong survival. For stage IV patients, the major therapeutic procedure is a CDV combination (cisplatin, dacarbazine, vindesine). Adoptive immunotherapy is almost always used for patients with distant metastases. They have shown comparable effects for metastatic lesion in the lymph nodes, mucous membrane, brain and lung. Excellent results were obtained in patients having skin metastases by intratumoral injection of interferon-beta. Studies on new drugs and their combinations must be undertaken for more effective treatment of malignant melanoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

[Radiotherapy of limited pulmonary microcytoma in current clinical practice].

The use of thoracic irradiation in the treatment of "limited disease" small-cell lung cancer yields better local control and survival rates than chemotherapy alone, according to meta-analysis studies of randomized clinical trials. Outside experimental studies, however, the role radiotherapy can currently play in the management of this type of cancer is difficult to assess because treatment modalities and patient selection criteria differ greatly. We report on the treatment outcome obtained in the Radiotherapy Department of the University of Siena in a series of 86 patients with small-cell lung cancer consecutively referred, January 1986 to January 1992; after a thorough staging, 46 of them were diagnosed as having a "limited disease". A "sequential" chemo-radiotherapy combination was used: irradiation was delivered after the completion of the initial drug treatment. Twenty-four patients (52.5%) achieved a complete and 22 (47.5%) a partial objective remission after chemotherapy, with acceptable early toxicity rates and severity. Twenty-eight of them received irradiation according to the following selection criteria: objective remission after chemotherapy (19 of 24 complete responders, excluding those with initial pleural effusion or worsening medical status during chemotherapy) and initial large tumor bulk (9 of 22 patients in partial remission). The overall treatment outcome rate (median survival: 18 months, 2-year survival: 28%) is in agreement with that of similar previous studies; toxicity rates are also similar (2% of treatment-related deaths). Survival analysis, according to "performance status" score, chemotherapy schedule and the achievement of complete remission with the initial drug management, exhibited significant differences only relative to the latter parameter. Many recent clinical trials suggest that combined chemo-radiotherapy could improve these results: toxicity is however reported as heavy, with this approach. Some guidelines are here considered, which could make this combination reliable also for current clinical use.

Aged↗
PubMed1995

[The use of an early postoperative interstitial-hyperthermia combination therapy in malignant gliomas].

BACKGROUND: The survival of people suffering from malignant gliomas (WHO level III and IV) is predominantly limited by local progress in the primary tumor region. Interstitial hyperthermia combined with radiotherapy or chemotherapy is one approach for the intensification of local therapy. It is possible to combine (partial) tumor resection with hyperthermia as well as with brachytherapy by implanting catheters intraoperatively. PATIENTS AND METHODS: A pilot study was performed to examine practicality, tolerability, effectiveness and scope for improvement in early postoperative hyperthermia treatment following catheter implantation as part of (partial) tumor resection. Each CT data set was transferred into a VAX 3100 workstation for retrospective analysis of the hyperthermia treatment. The implanted catheters were segmented and the distributions of power density and temperature were simulated. We sought to achieve the best possible temperature distributions by optimising the catheter arrangement in the planning calculations. The corresponding Ir-192-source brachytherapy treatments were simulated in a similar way using the implanted, as well as optimised catheter arrays. RESULTS: Intraoperative catheter implantation in 4 patients was problem-free. Postoperative complications were not observed, neither were infections. Interstitial microwave hyperthermia in combination with percutaneous irradiation or chemotherapy a few days after the operation was also tolerated well by all patients. Effective temperatures (of at least 42 degrees C) were regularly achieved at measurement points, but the temperature distributions were unsatisfactory, with T90 values (the temperature reached in at least 90% of the target volume) of under 38 degrees C. Measured temperature/position curves showed qualitative correlation with the simulated calculations. The catheter positions determined by optimisation varied significantly from the positions clinically used. CONCLUSIONS: Early postoperative combination therapy using hyperthermia for the treatment of malignant gliomas is a very practical approach. The optimisation strategies described should be used preoperatively to plan catheter arrays for interstitial hyperthermia and brachytherapy, and these arrays should be implanted using stereotaxic surgery.

Antineoplastic Agents↗
PubMed1993

[Chemotherapy of malignant melanoma].

Malignant melanoma is among the malignant tumors which still have the poorest prognosis. Thus, malignant melanoma of stage II and the more advanced stages. At present, chemotherapeutic combinations used as the first choice in Japan are two regimens of postoperative adjuvant therapy for stage II and III patients, that aim at preventing recurrence. One of the regimens is a DAV combination (Dacarbazine, ACNU, vincristine), and another is PAV combination (Pepleomycin, ACNU, vincristine). For stage IV patients, the major therapeutic procedure is a CDV combination (cisplatin, dacarbazine, vindesine). The efficacy of CDV treatment has been approximately 30 per cent in our studies. It has shown comparable effects for metastatic lesion in the lymph nodes, mucous membrane (nasal cavity) and brain, while lesions in other organs are largely unaffected in many instances. Studies of new drugs and combinations must be undertaken for the treatment of malignant melanoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Therapeutic effects of photosensitizers in combination with laser and ACNU on an in vivo or in vitro model of cerebral glioma.

This study investigated the independent and combined effects of photodynamic therapy (PDT), laser photodynamic hyperthermia (LPDH) and 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl) -3-nitrosourea hydrochloride (ACNU) in a rat 9L induced gliosarcoma model. The mortality rate (MR60), mean survival time (MST60), and increasing life span (ILS60) within 60 days were determined to evaluate the therapeutic effect in vivo. The MR60 and MST60 of the gliosarcoma tumor control were 100% and 16.2 days. The ILS60s of PDT and ACNU were 72.84% and 49.81%, respectively, but MR60 of both were 86.72%. All combined treatments produced significantly prolonged survival (P < 0.01). The combined effects of LPDH and ACNU, MR60, MST60, and ILS60 were 60%, 43 days, and 165.4%, respectively. The ILS60 of PDT + ACNU (96.48%) and PDT + LPDH (98.58%) also indicated a synergistic or additive effect. The survival fraction and synthetic rate of DNA, RNA, and protein of glioma 9L tumor cells in vitro after single treatment of PDT or combined with antitumor drugs and laser showed that the cytotoxicity of PDT to 9L tumor cell was obvious by using Rh123, HPD, and Pf-II as photosensitizers. Combined treatments of PDT, antitumor drugs, and laser suppressed the synthesis of DNA, RNA, and protein more significantly than single treatment with PDT.

Animals↗