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At least 235 records · Page 13Linked to original sources
PubMed1979

Human brain tumor transplantation into nude mice.

Seven human brain tumors were transplanted into the brains (6/7 takes) and subcutaneous tissues (7/7 takes) of athymic nude mice. Compared to experimental animal brain tumors, these tumors, taken directly from patients in the operating room and transplanted, grew more slowly in the mice; their growth rates following explant generally paralleled those in the patients. A rough correlation was seen between the degree of the tumor's malignancy and both successful take and rate of growth following explant. The tumors' growth rates increased during serial transplantation after explant. Two tumors developed into long-term serial lines; both came from gliosarcomas. Preliminary chemotherapy experiments with these two lines demonstrated different chemosensitivities. One line was very sensitive to the nitrosoureas and resistant to procarbazine; the other line was more sensitive to procarbazine than to the nitrosoureas. This model permits study of the biologic behavior of human brain tumors growing intracerebrally and subcutaneously in nude mice.

Animals↗
PubMed1994

Long term response to chemotherapy in patients with visceral metastatic melanoma.

PATIENTS AND METHODS: Eight patients who remain in long term remission 4 to 15 years after chemotherapy for visceral metastatic melanoma are described. These patients were observed among some 1100 patients with visceral melanoma seen at the Sydney Melanoma Unit between 1977 and 1989. Only about one-third of such patients received chemotherapy, almost always with single agent dacarbazine or a nitrosourea. RESULTS: The apparently cured patients did not differ from the overall group of patients with visceral metastases in baseline characteristics, but 6 of the 8 had nodular lung metastases. CONCLUSIONS: While the mechanism remains uncertain, one possibility could be that chemotherapeutic agents cause mutations which allow expression of antigenicity in tumour cells. In any case, the fact of occasional exceptionally good responses, perhaps amounting to cure, constitutes an argument for a trial of chemotherapy in patients with visceral metastatic melanoma.

Adolescent↗
PubMed1982

Phase II trial of methyl-CCNU, vincristine, 5-fluorouracil, and streptozotocin (MOF-Strep) in patients with disseminated pancreatic carcinoma.

A phase II trial of methyl-CCNU, 5-fluorouracil (5-Fu), vincristine, and streptozotocin (MOF-Strep) was conducted on 20 patients with pancreatic carcinoma. There were two partial remissions (10%) lasting 3 and 10 months. In addition, there were two minor responses. The predominant toxicity was gastrointestinal, although hematologic and renal toxicity were also seen. Since the response rate to MOF-Strep does not appear to exceed that to 5-Fu alone, the usefulness of this combination in patients with pancreatic carcinoma is limited.

Adenocarcinoma↗
PubMed1982

Sequential phase II studies of chemotherapy for colorectal cancer with 5-fluorouracil and vindesine with or without methyl-1,3 cis(2 chloroethyl)-1-nitrosourea.

Vindesine, a newer vinca alkaloid, has been demonstrated to have activity against colorectal cancer during phase I studies. This report describes the results of two phase II trials in which vindesine was administered with 5-fluorouracil (5-FU) or in combination with 5-FU and methyl-1,3 cis(2 chloroethyl)-1-nitrosourea (MeCCNU). One of 16 patients (6%) given 5-FU-vindesine, and 4 of 31 (13%) patients in the 5-FU-vindesine-MeCCNU group achieved partial response (PR). Stable disease was observed in 50% of the 5-FU vindesine and 48% of the 5-FU-vindesine-MeCCNU group. In each treatment group, survival of respondents and those with stable disease was statistically superior (p less than 0.02) to that of those with progressive disease; there was no difference however, in overall survival between the two treatment groups and no enhancement of survival compared to published reports of results with 5-FU alone. No chemotherapy-related deaths occurred and both treatment regimens were well tolerated. Myelosuppression, which occurred with equal (50%) frequency in both regimens, was the major dose-limiting toxicity. MeCCNU increased the incidence of gastrointestinal toxicity. Vindesine neurotoxicity occurred in approximately 4% of the evaluable courses in each group. Combination therapy with 5-FU vindesine with or without MeCCNU in the dosages administered did not significantly increase the activity of 5-FU. Further evaluation of vindesine will require dosage modification.

Adult↗
PubMed1982

Subacute vincristine toxicity following five consecutive daily doses.

Vincristine (VCR) is commonly included in combinational chemotherapy regimens because of its synergy with a variety of other active agents, as well as its sparing of the hematopoietic system. While acute toxicity is not infrequently reported, a recent experience in an adult who received five consecutive daily doses of VCR (1.0 mg/m2) in conjunction with two other drugs led to a sequence of life-threatening toxicities which were not obviously ameliorated by folinic acid rescue as has been recently advocated. The increasing administration of protocol chemotherapy by practitioners in the community, who may not be especially familiar with the particular agents in a given regimen, suggests such errors may become more common.

Adenocarcinoma↗
PubMed1984

Randomized trial of chlorozotocin, neocarzinostatin, or methyl-CCNU in patients with malignant melanoma.

One hundred twenty-two patients with disseminated malignant melanoma were randomized using an unbalanced randomization to receive chlorozotocin, neocarzinostatin, or MeCCNU. Of the 114 evaluable patients, 46 received chlorozotocin, 47 received neocarzinostatin, and 21 received MeCCNU. The response rates to these three drugs were 9%, 4%, and 14% respectively. Median survival times were 4.2, 3.4, and 5.8 months respectively. Toxicity was acceptable with all three agents. Chlorozotocin and neocarzinostatin do not appear to offer any improved response rates over MeCCNU for patients with disseminated malignant melanoma.

Adult↗
PubMed1985

Radiation therapy alone or in combination with chemotherapy in the treatment of residual or inoperable carcinoma of the rectum and rectosigmoid or pelvic recurrence following colorectal surgery. Radiation Therapy Oncology Group study (76-16).

Between 1976 and 1981, 147 patients with residual, inoperable, or locally recurrent carcinoma of the rectum were randomized to receive either radiation (XRT) alone or XRT plus chemotherapy (concomitant 5-FU during XRT and maintenance 5-FU + MeCCNU). An initial field received 4,500-5,100 rad in 5-6 weeks, with a boost field dose to a maximum of 7000 rad/8 weeks (maximum 6,000 rad/7 weeks with chemotherapy), dependent on findings of special small bowel films. One hundred twenty-nine patients were evaluable (65 XRT, 64 XRT + chemo). There were no statistically significant differences between treatments with respect to overall survival, complete remission rate, time to disease progression, local failure rate, or radiation dose distribution. Median survival was 17 months for XRT, 18 months for XRT + chemo; the 2-year survival probability was 36% for XRT, 44% for XRT + chemo. Initial performance status was a significant prognostic factor for both survival and time to disease progression. A trend was observed favoring the combination treatment for patients with residual disease. Treatment complications were greater for the combined modality arm than for radiation alone. Twenty-seven patients (22%) were alive at last data analysis, with no evidence of disease (NED) from 2-51 months (30 months median). Patients with resection of gross disease before or after irradiation had a much better result than those with gross residual or without any resection, but the relative influence of patient selection versus impact of surgery remains unclear.

Abscess↗
PubMed1985

Chemotherapy of large bowel carcinoma--fluorouracil (FU) + hydroxyurea (HU) vs. methyl-CCNU, oncovin, fluorouracil, and streptozotocin (MOF-Strep). An Eastern Cooperative Oncology Group study.

In this prospective randomized study of initial chemotherapy for advanced measurable metastatic large bowel carcinoma, the response rate was 6/32 (19%) for FU + HU and 5/32 (16%) for MOF-Strep; the estimated median survival is 43 weeks for both treatments. Patients who received MOF-Strep experienced substantially greater vomiting and hematologic toxicity than patients who received FU + HU (p less than 0.001).

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Methyl-CCNU and methotrexate therapy in patients with advanced colorectal cancer after failure of 5-fluorouracil chemotherapy.

Thirty-six patients with advanced colorectal cancer whose disease progressed during treatment with 5-fluorouracil (5-FU) chemotherapy were treated with methyl-CCNU and methotrexate. Five patients (14%) achieved a partial response (PR), three (8%) showed disease regression less than that required for a PR, and three (8%) showed evidence of stable disease. Twenty-five patients (69%) progressed on treatment. Tumor regression was seen only in patients with good performance status (ECOG 0.1). The median survival time of patients achieving a PR was 31 weeks. Those patients with stable disease or disease regression less than a PR had median survival times of 49 and 32 weeks, respectively. The comparable figure for those patients with disease progression was 17 weeks. Myelosuppression, principally in the form of leukopenia and thrombocytopenia, was common. Nausea and vomiting were universal with methyl-CCNU, and mucositis and diarrhea occurred commonly due to methotrexate. These results demonstrate the limited activity of chemotherapy in refractory colorectal cancer. They also reaffirm that poor pretreatment performance status should exclude patients from futile attempts at palliative therapy or phase II clinical trials, as these patients derive little or no benefit from them.

Adult↗
PubMed1986

The efficacy of 5-fluorouracil, mitomycin C, and methyl CCNU in advanced colorectal cancer.

Sixty-six patients with advanced colorectal cancer were treated with 5-fluorouracil, Mitomycin C, and 1-(2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea. Fifty-seven patients were evaluable by completing 2 months of therapy. Nine patients (16.0%) achieved a complete remission (CR) with the above combination. A partial remission (PR) was seen in 9 patients. The response rate (CR + PR) was 32%. The average duration of response was 8.5 months. Mucositis, leukopenia, and thrombocytopenia were the significant toxicities experienced in this study.

Adult↗
PubMed1987

Treatment of advanced colorectal carcinoma with actinomycin D, vincristine, methyl-CCNU, and methotrexate.

Twenty patients with advanced colorectal carcinoma were treated with combination chemotherapy consisting of actinomycin D, vincristine, methyl-CCNU, and methotrexate. Fourteen patients had received prior chemotherapy with 5-fluorouracil (5-FU). No complete responses and only one partial response were observed for an overall response rate of 5%. The combination of actinomycin D, vincristine, methyl-CCNU, and methotrexate at the doses and schedule used was of no value in the treatment of patients with metastatic colorectal carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1987

A randomized clinical trial of combination chemotherapy in advanced colorectal cancer.

One hundred and sixty-five patients with advanced colorectal cancer were entered into a prospectively randomized trial of combination chemotherapy comparing three 5-fluorouracil plus methyl CCNU (FM)-based regimens: FM plus ICRF-159 (FMI), FM plus triazinate (FMT), and FM plus vincristine (FMV). Patients were stratified according to performance status, anatomic site of primary indicator lesion, and prior chemotherapy. Those with abnormal kidney or liver function were randomized between FMI and FMV because triazinate depends on both hepatic and renal mechanisms for elimination. There were no significant differences between the treatment regimens in objective response rate (11%-17%), interval to progression (median, 10-14 weeks), or survival (median, 5-6 months). The primary side effect observed was hematologic toxicity, which tended to increase in severity with repeated courses of therapy. Although ICRF-159 and triazinate have been shown to have limited single-agent phase II activity against colorectal cancer in previous trials, neither agent combined with 5-fluorouracil plus methyl CCNU has an improved treatment effect compared with FMV. We do not recommend the further use of these regimens in the treatment of advanced colorectal cancer.

Adult↗
PubMed1988

Implementation of the group sequential methodology in a randomized trial in metastatic colorectal carcinoma.

A prospective randomized trial using the group sequential statistical method with frequent planned interim analyses was initiated in patients with metastatic colorectal adenocarcinoma comparing methotrexate and 5 fluorouracil (MTX-FU) to methyl CCNU, vincristine, FU, and streptozotocin (MOF-Strep). As a requirement of the group sequential design, a p value of 0.0125 was necessary to stop the trial at the first analysis. The first analysis was done after 17 patients were entered in each study arm and revealed six partial responses to MOF-Strep (35%) and one partial response to MTX-FU (6%) (p = 0.017). As a result, patient accrual continued. Problems encountered with the implementation of the group sequential methodology and the importance of stratification for prognostic variables are discussed.

Adult↗
PubMed1989

Activity of 5-fluorouracil, mitomycin C, and methyl CCNU in inoperable adenocarcinoma of pancreas.

Twenty-two patients with inoperable adenocarcinoma of the pancreas were treated with 5-fluorouracil (5-FU), mitomycin C (Mito-C), and 1(-2-chloroethyl)-3-(4-methylcyclohexyl)-1-nitrosourea (MeCCNU). Fifteen were evaluable by completing 2 months of therapy. Two patients achieved a complete remission with the above combination. A partial remission seen in four other patients, which produced a response rate of 40% of evaluable, and 27% of entered, patients. Three had stable disease. The average time to progression in this study was 8 months. This combination was well tolerated and no deaths were secondary to drug therapy. Mucositis, leukopenia, thrombocytopenia, and hyperpigmentation were the significant toxicities seen in this study. These observations are worthy of further investigation.

Adenocarcinoma↗