Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A total of 39 women with metastatic breast cancer entered a pilot phase II study of the vindesine-mitoxantrone-mitomycin (VMMc) combination chemotherapy. Most of them had received previous chemotherapy [including doxorubicin (27 patients)] for their primary or metastatic disease. The VMMc drugs were given at usual doses. Hematologic side effects were the most serious, leading mainly to leukopenia (five episodes of infection were successfully treated). A 33% partial response rate was obtained (95% confidence limits, 18%-48%), with a median duration (not yet reached) of greater than 510 days (range, 150-720) for the overall population. The median for pretreated patients was greater than 420 days (range, 150-720) which compares favorably with those previously reported in similar patients treated by mitomycin and vindesine or vinblastine.
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PMID:Long duration of response with vindesine-mitoxantrone-mitomycin (VMMc) combination chemotherapy in metastatic breast cancer: a pilot phase II study. 362 Dec 18

Thirty-six patients with adenocarcinoma or epidermoid carcinoma of the esophagus were entered into a phase II trial evaluating the combination of cisplatin 100 mg/m2 intravenously (IV) day 2, vinblastine 1.6 mg/m2 IV days 1 to 4, and mitoguazone (MGBG) 500 mg/m2 IV days 1 and 8. Twenty-nine patients (group A) were newly diagnosed with local-regional disease only and were candidates for transhiatal esophagectomy (THE). These patients received two courses of chemotherapy at 3-week intervals prior to surgery. Response was assessed by measuring changes in the primary tumor length and depth on serial biphasic contrast esophagrams and comparing this result with tumor measurements obtained from the surgical specimen. Complete (CR) and partial responders (PR) received three additional postoperative cycles. Seven patients had recurrent or metastatic disease (group B) and were treated every 4 weeks until disease progression. Of 34 patients evaluable for response, there was one pathologically confirmed CR and 15 PRs (47%). This consisted of 12 of 27 (44%) group A patients (seven of 11 epidermoid, five of 16 adenocarcinoma) and four of seven (57%) group B patients (two of four epidermoid, two of three adenocarcinoma). Toxicity included leukopenia in one third of treatment courses and thrombocytopenia in 21%. Nausea and vomiting occurred in 60% of patients, diarrhea in 18%, transient nephrotoxicity in 18%, peripheral neuropathy in 12%, and ototoxicity in 3%. Twenty-five group A patients underwent resection. Four chemotherapy nonresponders (NR) and one PR had known disease left at surgery; all others (80%) had gross total removal of their disease. The median survival time (MST) of the 29 group A patients was 14 months, with 21% alive at 36 months. The MST of group A chemotherapy responders was 15 months compared with 9 months for NRs (P = .032). Initial sites of recurrence in 14 patients were local-regional in six, distant only in six, both local-regional and distant in two. This regimen, administered in maximally tolerated doses, was active in epidermoid and adenocarcinoma histologies, recurrent disease and newly diagnosed patients. However, nearly all responses were PRs and the MST of resected patients was similar to a prior series of patients treated with esophagectomy alone. Observations from this pilot trial and those of others have led to a follow-up study, in progress, evaluating intensive preoperative chemotherapy and concurrent radiation therapy (RT).
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PMID:Cisplatin, vinblastine, and mitoguazone chemotherapy for epidermoid and adenocarcinoma of the esophagus. 362 44

Patients with a pathologically proven diagnosis of malignant melanoma were entered into a phase II trial of bisantrene. Eligibility criteria included: measurable, metastatic disease; performance status 0-2 SWOG; and adriamycin total cumulative dose of less than 400 mg/m2. The initial bisantrene dosing schedule was 260 mg/m2 every three weeks for good risk patients. Due to the absence of an objective response and the lack of severe toxicity in the first 25 bisantrene treated patients, the starting dose was increased to 300 mg/m2 for good risk patients. Fifty-one patients received a median of two bisantrene courses (range 1-11 courses). Leukopenia was the major toxicity. Fifteen (68%) of the 22 good risk, intermediate dose patients (260 mg/m2), and 8 (80%) of the 10 good risk, high dose patients (300 mg/m2) evaluable for toxicity experienced mild-severe leukopenia. None of the 51 patients experienced a complete or partial response to bisantrene. Median survival was 3.3 months. We conclude that bisantrene is ineffective in the treatment of metastatic melanoma.
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PMID:Phase II evaluation of bisantrene hydrochloride in refractory malignant melanoma. A Southwest Oncology Group Study. 366 64

Thirty-six evaluable patients with metastatic measurable breast carcinoma previously treated with CMF or CMFVP were given second-line chemotherapy with Adriamycin, vinblastine, and mitomycin C (AVM), as follows: Adriamycin 20 mg/m2 and vinblastine 6 mg/m2 by i. v. push on days 1, 8, and 15, and mitomycin C 10 mg/m2 i. v. on day 1, every 6 weeks. Ten patients (28%) achieved partial remission (PR) lasting a median of 10 months, and eight patients (22%) experienced improvement of a lesser level than PR. An additional nine patients (25%) had disease stabilization; in the remaining nine patients (25%), persistent disease progression was observed. The median survival from the onset of AVM was 7 months for all patients; patients with PR survived a median of 13 months. Myelotoxicity was substantial and frequently interfered with the optimal administration of AVM, especially in patients with skeletal metastases; four patients were hospitalized with leukopenia and fever; all recovered promptly; one death was probably related to thrombocytopenia and CNS bleeding. Our results with AVM are similar to the average response rate published in the literature with the use of Adriamycin as a single agent in previously treated patients with advanced breast cancer.
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PMID:Adriamycin, vinblastine and mitomycin C as second-line chemotherapy in advanced breast cancer. 379 61

Polyinosinic-polycytidylic acid, a double-stranded ribonucleic acid that is a potent inducer of interferon production, was used in a stabilized form to treat 11 patients with metastatic renal cell carcinoma. Seven patients completed a full course of 8 infusions at maximum tolerated dosage. All patients experienced transient fever and marked fatigue. Anorexia was mild. Transient leukopenia occurred in 3 patients and reversible elevation in creatinine was observed in 1. All 4 patients with brain metastases became lethargic, and 3 died during or shortly after therapy. Only 2 patients demonstrated measurable total regression of isolated metastases (pleural/pulmonary in 1 and bone in 1) but in both metastases at other sites progressed. No partial regressions were seen. Metastases at all other sites (liver, brain and renal fossa) progressed during therapy. Patients who appeared to respond and who performed best during therapy generally demonstrated a higher performance status initially. Expression of natural cytotoxicity in in vitro testing did not correlate with a demonstrated response to treatment.
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PMID:Immunotherapy of metastatic renal cell carcinoma with polyinosinic-polycytidylic acid. 380 4

Forty-four patients with non-small cell carcinoma of the lung were treated every 3 weeks with vinblastine (4 mg/m2/day iv X 2) and cisplatin (20 mg/m2/day iv X 3). Of the 28 patients with metastatic disease, eight (29%; 90% confidence interval of true response, 17%-47%) achieved objective response, for a median duration of 27 weeks. Median survival in this group was 47 and 28 weeks for responders and nonresponders, respectively. Of the 16 patients with advanced regional disease, 11 (69%; 90% confidence interval of true response, 49%-86%) achieved objective response. Thirteen of these patients received consolidation radiotherapy (4500 cGy/25 fractions/5 weeks), with a boost of 1000 cGy/5 fractions/1 week in those patients who achieved response. In the three patients who did not receive radiotherapy, two died during the induction phase, one from grade 4 leukopenia and sepsis and the second from unrelated factors. The third patient had systemic progression of disease during induction chemotherapy. Six patients experienced overall improvement in their chemotherapy response from the radiotherapy. Two patients who did not respond to the chemotherapy achieved partial response with irradiation. Four patients who had partial response to the chemotherapy achieved complete response with irradiation, and seven patients had no further change in their degree of response to irradiation. The overall median survival of this group was 81 weeks. Maintenance chemotherapy was not given. After radiotherapy, the site of first failure was outside the radiation field in nine of 13 patients (69%). Hematologic toxicity was dose-limiting. Other toxic effects that were not dose-limiting included nephrotoxicity, neurotoxicity, and acute nausea and vomiting. In the patients with advanced regional disease, there was no increase in the radiation toxicity attributable to the chemotherapy. We conclude that: (a) this dose schedule of vinblastine and cisplatin has reproducible activity in non-small cell carcinoma of the lung; (b) the response and median survival of patients with advanced regional disease are superior to those of patients with metastatic disease; and (c) in patients with advanced regional disease, treatment with chemotherapy followed by radiotherapy yielded an overall response rate of 81% (90% confidence interval of true response, 60%-93%) and improved survival compared to a similar group of patients studied by others receiving radiotherapy alone. We recommend further testing of this concept.
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PMID:Cisplatin and vinblastine chemotherapy for metastatic non-small cell carcinoma followed by irradiation in patients with regional disease. 395 44

The pharmacokinetics of isolated limb perfusion were studied to see what melphalan concentrations were achieved and how effective the isolation was. Twenty-eight patients received 32 limb perfusions with heat and melphalan for locally recurrent or level V melanoma. Melphalan was given 0.75 mg/kg for axillary/popliteal or 1.2 mg/kg for femoral perfusions with heat (perfusate 42 degrees C, limb 40 degrees C) for 1 hour. Melphalan concentratives were measured by high-performance liquid chromatography in seven patients. Peak perfusate melphalan concentrations were 6.1 to 115 mg/ml, which was one to two logs higher than peak systemic concentratives of melphalan. Isolation of the perfusate circuit from the systemic circulation was better for axillary and popliteal perfusions than for femoral perfusions (P less than 0.05). Complete responses were seen in 81% of evaluable patients; long-term local control was achieved in most patients, although many developed hematogenous metastases. Toxicity included erythema and edema in all, mild leukopenia in two, neuropathy in two, and amputation was required in one patient. Improvements in surgical technique include regional anesthesia to reduce vasospasms and transcutaneous measurement of fluorescein to measure leak. Perfusion with heat and melphalan remains the treatment of choice for in-transit metastases from melanoma.
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PMID:A clinical and pharmacokinetic study of isolated limb perfusion with heat and melphalan for melanoma. 399 75

Nine patients with advanced cervical cancer were treated with a combination chemotherapy (MVP) consisting of mitomycin C 8 mg/m2 i.v. days 1 and 8, vincristine 1 mg/m2 i.v. days 1 and 8, and cisplatin 15 mg/m2 i.v. days 1 to 5. The regimen was repeated at 4-week intervals. Of nine patients with measurable metastatic disease, there was 1 complete response (CR), 4 partial responses (PR), and 4 with no change, with an overall response rate (CR + PR) of 56% (5/9). The median duration of responses was 6 months, ranging from 1.8 to 9.1 months. The median survival time from initiation of the chemotherapy was 11 months for responders, and 15+ months for non-responders, respectively. Patients with no prior chemotherapy had a 60% (3/5) response rate and 2 patients out of 4 who had received prior chemotherapy responded; furthermore, metastatic lesions in extrapelvic regions (lung) responded well. Leukopenia less than 3,000/mm3 occurred in 68% of cases and the median nadir was 1,900/mm3 (700-2900). Thrombocytopenia less than 10 X 10/mm3 occurred in 37% of cases and the median nadir was 5.15 X 10/mm3 (3.2-9.0). Non-hematological toxicities were nausea and vomiting, renal dysfunction and peripheral neuropathy, but these were reversible and tolerable.
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PMID:[A combination chemotherapy using mitomycin C, vincristine and cisplatin (MVP) for advanced cervical cancer]. 400 84

Partially purified interferon alpha (IFN alpha) was administered to 50 patients with metastatic renal-cell carcinoma (RCC) studied for more than two years. Complete or partial remissions were observed in 26% of the patients. Duration of remissions range from two to 16 months (median, six months). No distinct prognostic factors were clearly identified in the responsive patients, but responses occurred more frequently in men with optimal performance status who had undergone nephrectomy and in whom the metastatic disease was confined to the lungs, pleura, or mediastinum. Leukopenia and granulocytopenia were useful markers of biological activity but did not predict tumor response. Side effects and toxicity at the dosage used (3 X 10(6) units intramuscularly daily) were well-tolerated and consisted predominantly of fatigue and asthenia. We concluded that IFN alpha is useful for palliating metastatic RCC, but no impact on survival was demonstrated. Further studies are required to determine the optimal dose, routes of administration, and treatment schedules.
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PMID:Phase II study of interferon alpha in metastatic renal-cell carcinoma: a progress report. 402 Apr 10

Recombinant human leukocyte (alpha) interferon was administered i.m. at the initial dose of 3 X 10(6) U/day to 27 patients with measurable metastatic renal cell carcinoma during the past 2 years. The results of 22 of these patients were evaluable. Three patients (13.6%) showed partial response; 3 patients (13.6%), minor response; 7 patients (31.8%), no change; and 9 patients (40.9%), progressive disease. Major toxicity consisted of fever (55.5%), anorexia (44.4%), malaise (22.2%), elevation of GOT/GPT (48.1%), leukopenia (44.4%) and thrombocytopenia (29.6%). When the 3 patients who showed stabilization (S) and the 2 patients who showed mixed effects (ME) among the 7 patients who showed no change are classified into the responded group, half the patients had some response to interferon. Characteristics of these responders (PR + MR + ME + S) were good performance status, relatively longer disease-free interval, metastases limited to the lungs or metastasis to lungs and one other organ excluding the liver, and frequency of interferon-induced thrombocytopenia. Interferon administration is still being continued to 4 patients on an outpatient basis, 5 patients are hospitalized and 13 patients have died. In conclusion, patients with pulmonary metastases seem to be the best responding group for interferon treatment in renal cell carcinoma and further trials, especially combined regimens with chemotherapy and/or other kinds of interferon should be tested.
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PMID:[The treatment of renal cell carcinoma with recombinant human leukocyte interferon]. 402 77


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