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PubMed1992

[Nitrosourea-induced lung diseases].

Nitrosoureas belong to the group of alkylating agents, and are increasingly used in the treatment of brain malignancies, due to their excellent penetration through the hemo-meningeal barrier. Since 1976, pulmonary toxicity from nitrosoureas has emerged as a significant problem, especially with BCNU, and 72 cases are available in the literature for review. While it is difficult to ascertain the exact prevalence of nitrosourea lung (estimate range between 1 and 20%), it is now clear that a direct relationship exists between cumulated exposure to the nitrosourea, and the likelihood of developing pulmonary toxicity. The clinical picture is that of a diffuse, severe fibrosis with hypoxemia. Histopathology, available in 55 reports, showed diffuse bland fibrosis. The outcome is poor with 67% of the patients dead by the time of publication. While we feel that corticosteroids should be tried for any possible beneficial effect, they seem to be of limited help.

Adult↗
PubMed1977

Brain Tumor Study Group: a survey of current activities.

Improvement in the treatment of patients harboring malignant glioma will probably be seen as small incremental changes as new modalities of treatment are proposed, tested, and substantiated. Uncontrolled phase II studies may provide hints of efficacy. However, the results must be substantiated in carefully controlled phase III evaluations. The Brain Tumor Study Group of the National Cancer Institute has demonstrated that mithramycin is not effective in the treatment of malignant glioma and the overall median survivorship experience is no different than the 23 weeks found in historic controls. Radiotherapy can bring about a meaningful increase in survival as can 1,3-bis(2-chloroethyl)-1-nitrosourea. The combination appears to produce more long-term survivors than either treatment above. Methyl-1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea does not appear to be additive to radiotherapy but is more effective than no therapy at all. Studies of the oncolytic effect of corticosteroids in contradistinction to their cerebral edema controlling effects are being done and will provide meaningful data on this important symptomatolytic therapy.

Brain Neoplasms↗
PubMed2006

[Comparison of the long term results between two conditioning regimens MCC and BuCy in chronic myelocytic leukemia after allogeneic stem cell transplantation].

OBJECTIVE: To observe and evaluate the long term survival of patients with chronic myelocytic leukemia transplanted with MCC and BuCy conditioning regimens. METHODS: Fourteen cases were treated with MCC regimen (Melphanlan 170 mg/m2 x d x 1, MeCCNU 400 mg/m2 x d x 1, CTX 60 mg/kg x d x 2) and the median follow up time was 6 years; 16 cases were treated with BuCy regimen (Busulfan 4 mg/kg x d x 4, CTX 60 mg/kg x d x 2) and the median follow up time was 4 year. RESULTS: All the patients were engrafted successfully. 4 of 10 patients examined in MCC group showed mixed chimerism at day 100 after transplantation, whereas only 1 of 12 patients examined in BuCy group showed mixed chimerism. All the patients became complete donor source later without any DLI. The 5-year disease-free survival rate was 71.4% for MCC group and 62.5% for BuCy group. The transplant related mortality and relapse rate were 21% and 7% for MCC group, whereas those were 25% and 12% for BuCy group, respectively. The regimen related toxicity was relatively lower in MCC group and the median duration of hospitalization was 39 days (25-55 days) for patients with MCC regimen, and 55 days (39-90 days) for BuCy regimen. CONCLUSION: MCC regimen has a partial ablative effect on CML and the long term disease-free survival is the same as that of BuCy regimen. In regard to the cost-effect efficacy, MCC regimen has a substantial advantage over BuCy regimen.

Adult↗
PubMed1976

Nitrosourea combinations in lung cancer.

BCNU, CCNU, and methyl-CCNU have undergone extensive trial in multiple drug combinations for bronchogenic carcinoma. The addition of a nitrosourea appears to be an improvement over cyclophosphamide used alone in oat cell carcinoma and over the two drug combination of cyclophosphamide and methotrexate in both adenocarcinoma of the lung and oat cell disease. Encouraging response rates have been seen in squamous lung cancer with multiple-drug combinations of a nitrosourea, an alkylating agent, vincristine, and bleomycin with or without adriamycin. The nitrosoureas have been easily incorporated, at reduced doses, into multiple-drug regimens with cumulative myelosuppression seen only when the interval between nitrosourea doses is less than 6 weeks. Conclusions about the ultimate role of these compounds in lunb cancer treatment must await (a) comparative trials of combinations with and without a nitrosourea, and (b) further exploration of new approaches to increase their therapeutic index.

Adenocarcinoma↗
PubMedDate not supplied

Adjuvant therapy for patients with colon and rectum cancer.

The National Institutes of Health Consensus Development Conference on Adjuvant Therapy for Patients With Colon and Rectum Cancer brought together surgeons, medical oncologists, radiation oncologists, gastroenterologists, other health care providers, and the public to address the issues regarding adjuvant therapy for colon and rectum cancer. Following 1 1/2 days of presentations by experts and discussion by the audience, a consensus panel weighed the evidence and prepared a consensus statement. Among their findings, the panel recommended that patients with Stage III colon cancer should receive adjuvant therapy with 5-fluorouracil (5-FU) and levamisole. Specific adjuvant therapy is not recommended for Stage II colon cancer patients outside of clinical trials. For rectal cancer, the panel recommended that adjuvant therapy combining chemotherapy and radiation therapy improves local control and survival for Stage II and III patients. The most effective combination at present appears to be 5-FU, methyl-CCNU, and high-dose pelvic irradiation. However, the use of methyl-CCNU outside of clinical trials is discouraged because of documented toxicities. The panel concluded that patients with Stage I colon and rectal cancers are at low risk of recurrence and do not warrant adjuvant therapy. The panel also recommended that the American Joint Committee on Cancer system for classifying stages of colon and rectal cancer, known as the TNM system, become the standard measurement used in clinical trials and in clinical practice.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Adjuvant 5-FU and MeCCNU improves survival following curative gastrectomy for adenocarcinoma.

During the 13-year period ending December 31, 1984, 51 patients treated by curative gastrectomy for gastric adenocarcinoma invasive beyond the submucosa were eligible to enter adjuvant chemotherapy trials. Twenty-one of 22 patients in the first treatment group (FMe) received 5-fluorouracil and a nitrosourea. The second group of eight patients received the same drugs plus Adriamycin (FAMe). Twenty-one patients were observed as surgical controls. Each adjuvant treatment group was subdivided into groups of patients with zero to four or five or more lymph node metastases for survival analysis. Fifteen patients were alive without evidence of disease at five years. Analysis of variance of survival times showed that lymph node status (P = 0.0001) and adjuvant chemotherapy (P = 0.01) were statistically significant prognostic variables. The FMe group had the best survival. A Fisher's exact test showed that the FMe group had a greater proportion of five-year survivors (P = 0.0217) than the no treatment arm. Patients with only zero to four positive lymph nodes in the FMe group had a statistically greater number of five-year survivors than patients in the no treatment arm (P = 0.0155). In this series, postoperative 5-fluorouracil and MeCCNU significantly improved the survival times of patients after curative gastrectomy for adenocarcinoma as compared with surgical controls.

Adenocarcinoma↗
PubMed1986

Emulsion and activated carbon in cancer chemotherapy.

Based on a lipid-absorbing ability of lymphatic capillaries, a fat emulsion containing anticancer agents was applied to selectively deliver more increasing amounts of anticancer agents into regional lymph nodes. The emulsions, in which the drug solution is contained as the innermost phase or as oily soluble drug, yield high drug concentrations in the lymphatic system. Clinical trial of the emulsion method was carried out preoperatively for 180 patients with stomach cancer. As a result, the emulsion enhanced the chemotherapeutic effect of the anticancer agent on lymph node metastasis. About a 20 m mu-sized activated charcoal, in which anticancer agents were absorbed, selectively delivered the anticancer agents to the lymphatic system. The activated charcoal was also excellent carrier material for the lymphatic system, and we have applied it to patients with lymphatic metastasis.

Administration, Oral↗
PubMed1987

[Current status of diagnosis and treatment of metastatic liver cancer].

Clinical usefulness of liver function tests, tumor markers including CA 19-9, CEA and serum ferritin and image diagnosis was discussed in regard to early diagnosis. Liver function tests were not useful, and tumor markers were highly positive, i.e., CA 19-9 was positive in 70.7% and CEA in 66.7%. However, these were low positive rate, in the early stage. Imaging techniques were very useful in detecting liver metastasis; US positive in 92.5%, CT 87.2% and angiography 93.1%. In the treatment of metastatic liver cancer, arterial chemotherapy and transarterial embolization are the major modality.

Angiography↗
PubMedDate not supplied

Cytotoxicity and DNA damaging effects of a new nitrosourea, fotemustine, diethyl- 1-(3-(2-chloroethyl)-3-nitrosoureido) ethylphosphonate-S10036.

Fotemustine is a new chloroethylnitrosourea which has recently entered a Phase II clinical trial. Using standard cytotoxicity analyses, Fotemustine was shown to be preferentially active in two Mer- cell lines, human colon BE and human lung A427. Comparative cell kill in the Mer+ counterparts HT29 and A549 (respectively) was significantly lower. In a mouse cell line, P388, alkaline elution studies showed that Fotemustine caused fewer DNA strand breaks and total crosslinks (including DNA-protein) than either BCNU or MeCCNU at equivalent cytotoxic concentrations. In addition, the removal of DNA damage caused by Fotemustine was more rapid than of damage, three times as much Fotemustine was required. These data suggest that the cytotoxic mechanism of Fotemustine, although subject to the same repair mechanisms as other nitrosoureas, may not be entirely dependent upon DNA as the sole drug target. The previously reported reduced mutagenicity of this agent may also be a function of the less extensive nucleic acid damage. The encouraging early clinical trial results with this drug may reflect its improved pharmacokinetics and bioavailability, rather than any significant modification in its cellular pharmacology when compared to other nitrosoureas.

Antineoplastic Agents↗