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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The clinical trials of immunotherapy of renal carcinoma have been based on the theory that manipulation of the host-immune response can influence the growth of malignant cells in the host. The results cited above do not demonstrate a clear therapeutic role of immunotherapy but they do provide evidence to encourage further studies. This is especially pertinent in view of the current absence of effective systemic agents. The stimulation of the host response appears to be finite and cannot be expected to control massive tumor burden. The clinical trials analyzed above must be interpreted with this understanding. It remains necessary to test new approaches in patients with measurable disease, but stimulation of the immune response is finite and immunotherapy is probably best utilized as systemic adjuvants or in patients with limited metastases. However, the paramount task of those interested in immunotherapy of renal carcinoma remains adherence to the proper progression from Phase I to Phase II and finally to randomized Phase III trials. The natural history of this tumor confounds interpretation of many studies and can only be placed in proper context through the randomized trial mechanism. In the analysis of results of immunotherapeutic and other trials of advanced renal cancer, more careful attention must be given to the specific nature of the patient's disease. In all of the trials discussed above, responses were noted primarily in patients with limited pulmonary metastases. Indeed, since it is necessary that measurable disease be present for inclusion into most trials, this type of patient is the one most commonly treated. It is this group of patients who are most likely to undergo spontaneous regression or to have prolonged periods of stabilization without any other treatment. In addition, the impact of adjunctive nephrectomy in these patients must be clarified. The pulmonary metastases seem to behave differently than lesions at other sites and certainly seem to respond to almost any form of therapy far better than lesions at other sites. The significance of stratification of patients in randomized Phase III trials is therefore obvious and a true understanding of the therapeutic implications of our interventions can only be substantiated by careful randomized studies.
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PMID:Immunotherapy of renal cell carcinoma. 620 9

In patients with metastatic hormone-relapsed adenocarcinoma of the prostate, adriamycin was compared to 5-fluorouracil in a randomized trial in 99 patients and adriamycin alone was studied in an open trial in 48 patients. Response to adriamycin was superior as judged by response of measurable disease (25 vs 8%; P less than 0.05) and survival (median 29 vs 24 weeks; Cox analysis, P less than 0.03), but comparable as judged by acid phosphatase response. Ambulatory status and site of metastases influenced rate of response to chemotherapy. Activity level, site of metastases, weight loss, and the symptom of protein aversion were prognostic factors for survival. Hematologic and gastrointestinal toxicity were frequent but were tolerated satisfactorily. Adriamycin therapy may be beneficial in patients with prostatic cancer after hormone therapy.
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PMID:A comparative clinical trial of adriamycin and 5-fluorouracil in advanced prostatic cancer: prognostic factors and response. 634 81

Over a 24-month period, the Southwest Oncology Group (SWOG) conducted a randomized prospective chemotherapeutic trial in 158 patients with advanced prostatic cancer. Patients were initially randomized to receive either a combination of Adriamycin and cyclophosphamide (AC) or a single agent, hydroxyurea (H), and then crossed over to the other treatment on failure. Of the 137 evaluable patients, 43 (31%) had classically measurable metastatic disease in the lymph nodes, skin, chest, or liver. Focusing their efforts on this subset of patients with measurable disease, the authors of this report found the combination AC to have a superior response rate to the single agent, hydroxyurea. Objective response to AC was seen in 6 of 19 (32%) and in only one of 24 (4%) patients randomized to hydroxyurea (P = 0.06, Fisher's exact test). However, in the larger group of 137 evaluable patients, a survival advantage was not seen for those individuals treated with AC. Failure to demonstrate a survival advantage for an objectively superior drug combination would suggest the need for more active phase II agents in this disease.
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PMID:Adriamycin and cyclophosphamide versus hydroxyurea in advanced prostatic cancer. A randomized Southwest Oncology Group study. 636 15

In order to assess the value of the clonogenic assay for predicting clinical response to dimethyl-triazeno-imidazole-carboxamide (DTIC) plus hyperthermia (42 degrees C), the responses of patients with measurable disease, who received combined therapy, were compared with assay results. The clonogenic assay was used independently to determine in vitro sensitivities of 53 melanomas to DTIC, with and without hyperthermia. Separate cell suspensions were incubated for 1 hour with DTIC at 37 degrees C and at 42 degrees C. In vitro sensitivity was determined by inhibition of colony formation in a double-layer agar system. Three of the 53 (6%) melanomas were sensitive to DTIC at 37 degrees C, 13 of the 53 (25%) were sensitive to 42 degrees C hyperthermia alone, and 22 of the 53 (42%) were sensitive to DTIC at 42 degrees C. Nine patients were treated with DTIC, plus hyperthermia, to the areas of their melanoma metastases (one pulmonary, four hepatic, and four subcutaneous). In five patients, the clonogenic assay results predicted positive tumor sensitivity to combined therapy, and 4 of the 5 had objective tumor regression. Tumors were resistant in vitro for four patients, and all had disease progression during treatment. Statistical analysis suggested that some responses were due to synergism of the combination of heat and drug, whereas others were due to an additive effect. The apparent direct correlation between in vitro tumor cell sensitivity to DTIC at 42 degrees C and actual clinical response to chemotherapy, plus hyperthermia, in this limited trial, has been encouraging. The clonogenic assay and in vitro evaluation of drug-heat interaction may prove helpful for selecting those patients in whom hyperthermia should be used as an adjunct to chemotherapy, and may help determine the most effective drug/heat scheduling. Further trials with other malignancies and other chemotherapeutic agents are warranted.
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PMID:Predictability of response to clinical thermochemotherapy by the clonogenic assay. 661 4

A phase II clinical trial was set up in metastatic breast cancer patients who had not received previous cytotoxic drug therapy, involving the administration of cis-dichlorodiammine platinum (cis-DDP). Patients aged up to 75 years and with pathohistologically confirmed disease were entered on the trial. All patients had measurable disease, a performance status (Karnofsky) of greater than 40, and an expected survival of greater than 6 weeks. In all 38 patients entered the trial, and 35 have been evaluated. The predominating metastatic sites included soft tissues (19), visceral organs (12), and bones (7 patients). cis-DDP was administered in a daily dose of 30 mg/m2 IV by a 4-h drip for 4 days, with customary hyperhydration. The results indicate a pronounced antitumorigenic effect of cis-DDP and a response rate of 54% (19/35), with 13 complete remissions (37%) and six partial remissions (17%). In terms of site the best response was obtained in soft-tissue processes (13/19; 68%), followed by visceral organs (4/10; 40%); the response rate was lowest in bones (2/6; 33%). The menopausal status and prior hormone therapy did not essentially influence the results of treatment, unlike previous irradiation. Patients with a lower performance status (40-70) had a significantly lower response rate (36% vs 63%; P less than 0.05). Toxic side-effects were moderate and did not substantially affect the general condition of the patients. A transient increase of serum creatinine was observed in 4 patients, and neurotoxicity in 2 patients. The results of the trial warrant the conclusion that cis-DDP has a pronounced antitumorigenic effect in untreated metastatic breast cancer, particularly in soft-tissue metastases. These results call for additional clinical study of the cytotoxic effect of cis-DDP in untreated metastatic breast cancer.
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PMID:Phase II clinical trial of cis-dichlorodiammine platinum (cis-DDP) for antitumorigenic activity in previously untreated patients with metastatic breast cancer. 668 1

The prognostic value of pretreatment information relating to prior treatment, demography, physical status, symptoms, disease involvement, pathologic, immunologic, and clinical chemistries were analyzed for a series of 322 patients with advanced gastric cancer. All patients received chemotherapy upon entry into Gastrointestinal Tumor Study Group protocols which were active between 1975 and 1978. Multivariate models were used to study relationships between prognostic factors and survival for all patients and objective tumor resonse for a subset of 137 patients with measurable disease. The initial performance status was a leading determinant of survival (P less than 0.0001). In addition, new summary measures relating to blood chemistries (P less than 0.01) and differential counts (P less than 0.001) were shown to influence patient survival. Blood chemistry parameters included SGOT, total serum protein, and total direct bilirubin while differential counts included absolute granulocytes, lymphocytes, and monocytes. Thus, the initial performance status, measurable disease status, blood chemistries, and differential counts are recommended as stratification factors in the design and analysis of trials involving patients with advanced gastric cancer. The initial performance status was examined in relation to other pretreatment data. The performance status at study entry correlated independently with the degree of weight loss (P less than 0.001), blood chemistries (P less than 0.01), differential counts (P less than 0.05), and peritoneal metastases (P less than 0.05). The measurable and nonmeasurable subgroups were compared with respect to baseline characteristics. Patients with measurable disease had more liver metastases (56 versus 35%) and less peritoneal metastases (76 versus 49%) than patients with nonmeasurable disease. Controlling for the imbalance in liver and peritoneal metastases, the presence of measurable disease was less favorable than nonmeasurable disease with respect to survival. Regarding the pathways of disease spread, there was a strong correlation (P less than 0.001) between primary tumor site within the stomach and location of metastases. Diffuse lesions were associated with the lowest frequency (25%) of liver metastases. Diffuse lesions (58%) and tumors of the pyloris (54%) were associated with the highest percentage of peritoneal metastases. Tumors of the cardia or fundus were more likely to metastasize to the liver while diffuse tumors were more likely to spread to the peritoneum. Pretreatment factors under study did not appear to be the dominant factors responsible for prolongation of survival in patients with an objective tumor response. Pretreatment factors predicted a three week advantage; however, a 22 week advantage was observed for responders over nonresponders.
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PMID:Studies in prognostic factors relating to chemotherapy for advanced gastric cancer. 675 15

Sixty patients with renal adenocarcinoma have been treated with five different immunotherapy trials consisting of 1) Transfer Factor (TF), 2) TF and Bacillus Calmette-Guerin (BCG), 3) TF, BCG, Chloroethyl-cyclohexy-nitrosurea (CCNU) and megestrol acetate (Megase), 4) BCG, CCNU, and Megase, or 5) BCG. Using strict response criteria for measurable disease, objective responses were seen in 14-22% of cases. While this nonspecific immunotherapy of renal adenocarcinoma has been associated with documented regression of metastases, response rates are similar to that obtained with hormonal therapy alone. Objective responses support the concept of further trials in this disease with more sophisticated immunotherapy.
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PMID:A critical review of immunotherapy of disseminated renal adenocarcinoma. 710 37

Selection and determination of the efficacy of antineoplastic agents has been dependent upon the trial and error method of observing measurable disease. Such methods subject the patient not only to loss of precious time but to needless toxicity if the drug is ineffective. The clonogenic assay, an in vitro assessment of tumor cell sensitivity to antineoplastic agents, has the potential for individualizing therapy. In this assay, tumor cells exposed to various drugs are cloned in soft agar. In the 16 primary and 24 metastatic pulmonary tumors tested with this technique, a growth rate of 80% was achieved. Fifty-five percent of the primary tumors and 60% of the metastatic lesions responded in vitro to one or more of the test drugs. There were twelve possible correlations between in vitro and in vivo results. In four of 12 assays, in vivo sensitivity was predicted and three of four patients demonstrated a clinical response. No drug that was inactive in vitro had activity in vivo. Prior knowledge of in vitro sensitivity may dictate a more aggressive surgical approach to pulmonary metastatic disease, whereas in vitro resistance would call for more conservative treatment. Just as with estrogen receptor status in breast cancer, data derived from the clonogenic assay may ultimately be of such import that thoracotomy would be warranted solely for the purpose of obtaining tissue for the assay.
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PMID:In vitro assessment of antineoplastic therapy. New indication for thoracotomy? 727 44

Between 1972 and 1979, forty-six women underwent endocrine ablative surgery, having failed combinations of chemotherapy, radiation, and surgery (including oophorectomy). All had clinically measurable disease; nearly half were afflicted with bone pain. Each was judged to be a candidate for the procedure by estrogen receptor studies (52%), response to L-dopa (39%), or response to prior oophorectomy (8%). All were followed to their death or to the present, with a minimum of 12 months for those alive. Thirty-one (67%) were improved, and disease was arrested in five (11%) for a median time of 13.5 months. There was no difference in response rates or intervals between estrogen receptor-positive and L-dopa-positive groups. Response was not correlated with disease-free interval or menopausal status. Best results were achieved in those with metastases confined to an organ system, particularly the skeletal complex. The procedure is withheld in those with brain metastases. Postablative chemotherapy appeared to prolong the control interval, though numbers are small. The low morbidity and mortality (one death) of midline adrenaloophorectomy combined with the high incidence of recapture of disease leads us to recommend this procedure in appropriately selected patients who have previously failed other therapeutic modalities.
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PMID:Endocrine ablation in breast cancer patients who have failed cytotoxic therapy. 731 51

The objective of this phase I trial was to determine the maximal tolerated dose (MTD) of Taxol and doxorubicin administered as a simultaneous intravenous infusion over 72 hours every 21 days. Granulocyte-colony stimulating factor (G-CSF) 10 micrograms/kg, was administered on days 4-18 of each cycle. The treated population consisted of metastatic breast cancer patients previously untreated with chemotherapy for metastatic disease, who had not received doxorubicin in the adjuvant setting and who had bidimensionally measurable disease. The MTD was determined to be 75 mg/m2 of doxorubicin and 160 mg/m2 of Taxol. The dose-limiting toxicity of the combination was clinical typhlitis in three of three patients. Other significant toxicities included grade 3 diarrhea at the higher dose levels and grade 4 neutropenia in all patients. Eighteen patients were treated on this initial phase I study. The overall response rate was 62%, with 6% complete responses and 56% partial responses. The combination of doxorubicin and Taxol by 72-hour continuous infusion with G-CSF is an active regimen in patients with metastatic breast cancer.
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PMID:Phase I study of Taxol, doxorubicin, plus granulocyte-colony stimulating factor in patients with metastatic breast cancer. 751 54


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