Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0677930 (primary tumor)
 20,210 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with metastatic renal cell cancer have an overall 5-year survival rate of only 28% to 40% in spite of aggressive surgical treatment. A prospective randomized study conducted by the Eastern Cooperative Oncology Group used methyl--CCNU (meCCNU), vinblastine, and meCCNU-medroxyprogesterone acetate (MPA) to treat 165 patients with advanced renal cancer. The antitumor activity of the single-agent and/or combination therapy is analyzed. Patients were classified (as to grade of anaplasia of tumor; age; performance status; primary site of metastatic disease; and previous treatment with a progestational agent) and randomly assigned to various treatment protocols as described. Crossover randomization to one of alternate single-agent or combination regimens was carried out after failure with initial therapy. 2 meCCNU regimens were associated with severe hematologic toxicity, vinblastine regimens with neurotoxicity. All regimens except the vinblastine-MPA resulted in substantial vomiting. Response rate is low (11%) with each regimen. There were no statistically significant differences in treatment variables or factors among the various regimens. Patients capable of normal activity had a significantly higher response rate and longer survival period than nonambulatory or poor performance status patients. A relatively long symptom-free interval from primary tumor to metastatic disease was also associated with better survival rate. More than 50% of patients exhibited disease progression with 3 months of initiating the regimens.
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PMID:Phase II study of vinblastine, methyl-CCNU, and medroxyprogesterone in advanced renal cell cancer. 35 71

CGP 6809 is a water-soluble nitrosourea derivative with quite distinct chemical and biological properties as compared with the well-known representatives of this class of compounds. It is related to the antibiotic streptozotocin, from which it is distinguished in the structure of the sugar moiety and the position of the methylnitrosourea residue. CGP 6809 possesses practically the same alkylating potential as streptozotocin; however, its carbamoylating activity is comparable with that of CCNU. In contrast to other nitrosourea derivatives, CGP 6809 showed relatively little activity in murine leukemias but was markedly active in solid transplantable melanomas (Harding-Passay, B16), in the 11095 prostate carcinoma, and in a substrain of Yoshida hepatoma (AH 7974) resistant to BCNU and CCNU. In the Ehrlich and Yoshida ascitic tumors complete responses were seen with no toxic death. Dose-dependent activity was found in the human lung carcinoma MBA 9812 and almost complete growth inhibition was achieved in the human melanoma WM 47 by both the oral and parenteral routes of administration. However, mammary tumor lines (Ca 755, 2661/61, R-3230AC), the Guerin-T8 uterus epithelioma, and the Rous sarcoma/S-R proved to be relatively refractory to this drug. This was also the case for the Lewis lung carcinoma implanted i.m. or s.c. However, development of lung metastases was markedly inhibited. Combination therapy using CGP 6809 with cyclophosphamide, 5-fluorouracil, or chlorambucil in the same model led to partial responses of the primary tumor as well as almost total eradication of lung metastases.
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PMID:CGP 6809, a sugar-containing nitrosourea derivative: pharmacological and physicochemical properties. 271 56

Patients with limited-stage small-cell carcinoma of the lung (SCCL) were randomly assigned to a four-drug chemotherapy program consisting of methotrexate, doxorubicin, cyclophosphamide, and CCNU (MACC) or to a regimen consisting of cyclophosphamide, CCNU, and vincristine alternated with Adriamycin (Adria Laboratories, Columbus, Ohio) and vincristine (CCV/AV). All patients received 4,500 cGy, in a split course, to the primary tumor, mediastinum, and supraclavicular lymph node drainage areas and 3,000 cGy to the whole brain. After four cycles of chemotherapy, patients were randomly assigned to chemotherapy plus methanol extractable residue of BCG (MER-BCG) or no MER-BCG. The complete response frequencies were similar for the two regimens (54% and 48%) as were the median survivals (12.0 and 11.5 months) and the two-year survival rates (15% and 17%). Immunotherapy with MER-BCG did not prolong the time to disease progression or improve survival. Women had a greater chance of achieving a complete remission independent of performance status. There was a complex interaction between sex and the chemotherapy regimens that may have important implications for the design and stratification of future trials in SCCL.
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PMID:Combined modality therapy with radiotherapy, chemotherapy, and immunotherapy in limited small-cell carcinoma of the lung: a Phase III cancer and Leukemia Group B Study. 299 78

The Lewis lung carcinoma, implanted in the footpad of BDF1 mice, was used for testing a preoperative chemotherapeutic treatment in comparison to a postoperative one, or to surgery alone. We administered both drugs effective in this model (Cyclophosphamide, Ifosfamide, CCNU), as well as ineffective ones (Ftorafur, Methyl-GAG, Vincristine) in order to study all the possible influences on the treatment outcome. In nine different experiments one active and one inactive drug were always compared in various schedules. Groups with surgery alone at an early or later stage were used as controls. The results showed that preoperative adjuvant treatment with an active drug decisively improved the survival time and the number of cured animals compared to surgery alone. The administration of an inactive drug and postponement of surgery decreased the number of cures, while the lifespan of the animals dying from lung metastases was not influenced. An improved treatment outcome compared to surgery alone resulted in cases where the preoperative inactive treatment was replaced by postoperative treatment with an active drug-a procedure also common and applicable for clinical practice. The body weight of the animals, noted as a sign of toxicity, was lowered when a cytostatic drug was used in addition to removal of the primary tumor. There was no difference between pre- or postoperative and repeated administrations. Based on these results preoperative adjuvant cytostatic treatment with histological control of response and decision for postoperative adjuvant treatment is recommended for clinical practice.
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PMID:Preoperative (neoadjuvant) chemotherapy in the murine Lewis lung carcinoma and possible implications for clinical use. 359 36

Medulloblastoma is the most common primary tumor of the CNS in childhood. Surgical intervention alone will not cure this tumor, and the addition of whole neuraxis irradiation has led to a 50 to 60 per cent, 5-year survival. The role of adjuvant chemotherapy is unclear, although certain subgroups of high-risk patients may benefit from this modality. Agents that have demonstrated activity against recurrent disease include vincristine, cyclophosphamide, cisplatin, methotrexate, dibromodulcitol, and the combination of procarbazine-vincristine-CCNU. However, responses are generally transient and virtually no cures are reported. New, rationally selected agents are clearly needed. In vitro and in vivo models of human medulloblastoma using the medulloblastoma-derived cell lines TE-671 and D283 Med may allow such an approach. Phase II trials using the drugs effective in these models may identify active agents that will ultimately increase survival when used in an adjuvant setting.
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PMID:Rational approaches to the chemotherapy of medulloblastoma. 390 99

Thirty three evaluable patients with locally advanced squamous cell carcinoma of the lung were entered in a Phase II study combining chemotherapy (Vindesine 1.5 mg/m2 dl; CCNU 50 mg/m2 d2, 25 mg/m2 d3; Cis-Platinum 100 mg/m2 d3; Cyclophosphamide 200 mg/m2 d3, 4, 5) (VCPC) and radical radiotherapy to the primary tumor, mediastinum and supraclavicular nodes. Responders to chemotherapy resumed four additional cycles following radiation therapy. Fourteen patients (42%) presented an objective response to the first two cycles of VCPC. On final evaluation, 18 patients (54.5%) obtained a complete remission and 6 patients (18%) a partial remission. Median survival of all patients was 15.9 months and toxicity was acceptable. We conclude that our results justify a phase III study comparing combined treatment versus radiotherapy alone.
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PMID:[Inoperable lung epidermoid cancer non metastasizing. A phase II trial using radiotherapy and combined chemotherapy]. 403 6

Eighteen patients with unresectable carcinoma of the stomach whose known malignant disease was confined to structures immediately adjacent to the primary tumor and could be encompassed within a radiotherapy field were treated with an intensive sequential combined modality regimen. The regimen consisted of 5-FU plus adriamycin chemotherapy, followed by high dose megavoltage radiation therapy with 5-FU given as a radiation sensitizer, followed by maintenance chemotherapy with 5-FU plus adriamycin plus methyl CCNU (FAMe). Our primary objective was to determine patient tolerability. Severe and prolonged anorexia, nausea, and decreased performance status occurred during and after high dose radiotherapy given twice daily in 150-170 cGy (rad) fractions when given with 5-FU. Lengthening intervals between treatment segments, and the use of one daily dose of radiation therapy combined with 5-FU or two fractions daily without 5-FU seemed to decrease nutritional complications. Control of tumor at the primary site appeared to be achieved in most patients. Distant metastases represented the predominant mode of treatment failure with only two patients currently without progression of malignant disease. Our treatment regimen as initially conceived was too toxic for general use. Improved therapeutic results in locally unresectable gastric cancer will require the development of more effective therapy for occult distant metastases.
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PMID:A pilot study to determine clinical tolerability of intensive combined modality therapy for locally unresectable gastric cancer. 404 45

With the objectives of improving response rate, duration of response, and survival in small-cell carcinoma of the lung, 39 patients were randomized to remission-induction with either one of two potentially non-cross-resistant drug combinations: APE (consisting of adriamycin, 35 mg/m2 IV, D1 Q 3 weeks; procarbazine, 60 mg/m2 PO, D1-10 Q 3 weeks; and the epipodophyllotoxin (VP16-213), 130 mg/m2 IV, D8, 15 Q 3 weeks) or MOCC (composed of methotrexate, 15 mg/m2 IV (with [vincristine] Oncovin) or PO twice weekly D8-21 Q 3 weeks; Oncovin, 1.5 mg/m2 IV, D8, 15 Q 3 weeks; cyclophosphamide, 600 mg/m2 IV, D1 Q 3 weeks, and CCNU, 60 mg/m2 PO Q 6 weeks). A fixed crossover to the alternate regimen occurred at three months. Radiotherapy was delivered to the primary tumor (locoregional disease only) by a split course technique (1,750 rads for five days with a three-week split, followed by 3,400 rads over 17 days). The median survival including both arms was 11 months for regional and nine months for extensive disease. The chemotherapeutic activity of both regimens was comparable, with 15/17 (88 percent) of the patients responding to APE (including six complete) and 14/17 (82 percent) responding to MOCC (including five complete). The median survival for the complete responders was 11.7 months, while the partial responders survived for a median of 9.7 months. There were 2/9 (22 percent) responders to the alternate regimen at progressive disease. The overall incidence of CNS progression was 17 percent. The toxicity of the regimens was moderate, except for one instance of granulocytopenic death. This study establishes two equipotent drug combinations for the treatment of small-cell carcinoma of the lung.
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PMID:A controlled clinical trial testing two potentially non-cross-resistant chemotherapeutic regimens in small-cell carcinoma of the lung. 625 71

The antineoplastic activity of vindesine was evaluated in a phase II trial in patients with small cell anaplastic bronchogenic carcinoma. All patients had been treated previously with vincristine, CCNU, cyclophosphamide, VP-16-213, methotrexate, and doxorubicin. In some of the patients, the primary tumor had also been irradiated, and some patients had received 5-FU or procarbazine. The dose of vindesine was 4 mg/m2/week iv, modified according to hematologic and neurologic side effects. Twenty-six of 32 patients included in the trial were evaluable. Objective response was observed in seven patients (27%). The median duration of response was 35 days (range, 28-90), the response occurring within 14 days after initiation of treatment. Dose modification of vindestine was necessary in 80% of the patients because of hematologic toxicity, while neurotoxicity made dose reductions necessary in about one half of the patients. The study demonstrates that vindesine is active against small cell bronchogenic carcinoma, with apparent lack of clinical cross-resistance to vincristine in previously heavily treated patients.
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PMID:Vindesine in the treatment of small cell anaplastic bronchogenic carcinoma. 626 69

Between 1975 and 1979, 271 patients with regional small cell undifferentiated (including oat cell) carcinoma of the lung were entered into a study involving treatment by radiation therapy (4500 cGy (rad) in five weeks) to the primary tumor, mediastinum and supraclavicular lymph nodes, and a randomization to receive or not receive prophylactic treatment of the brain (3000 cGy in two weeks) and a randomization to prophylactic or delayed chemotherapy (cyclophosphamide and CCNU). Analysis of the data indicates that the median survival for responders (53 weeks) was significantly longer than that of the non-responders and partial responders (37 and 34 weeks). Median survival by treatment arm was 48 weeks for thoracic irradiation (TI), brain irradiation (BI), and early chemotherapy (CT), 44 weeks for TI alone, 41 weeks for TI and CT, 38 weeks for TI and BI. Regional complete and partial tumor responses were 52 and 25% for prophylactic chemotherapy and 44 and 35% for delayed chemotherapy. The site of first failure was regional in 12%, regional and distant simultaneously in 21%, and distant only in 46%. Elective brain irradiation significantly reduced the incidence of brain metastases from 21 and 5%, but did not improve survival.
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PMID:Combined modality treatment of regional small cell undifferentiated carcinoma of the lung: a cooperative study of the RTOG and ECOG. 630 41


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