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)

Twenty-seven patients with osteosarcoma and measurable metastases were treated with low-dose methotrexate (LDMTX) (80 mg/m2), followed by high-dose methotrexate (HDMTX) (7.5 g/m2) after disease progression in 14 patients. LDMTX was administered on Days 1, 8, and 15; if response or stable disease occurred, it was repeated on Days 29 and 43. If response occurred by Day 57, LDMTX was continued every 2 weeks until disease progression. If stable disease occurred by Day 57, the patient crossed over (optional) to HDMTX. HDMTX was given weekly during the first 3 weeks and continued once every 14 days until disease progression. Twenty-five of the patients were evaluable for response. Three patients (12%) achieved complete remission, with durations of 5, 14, and 34 weeks, respectively. The time to disease progression from the start of treatment was 19, 28, and 42 weeks. Twelve patients (48%) had stable disease, with a median duration of 7.5 weeks (range, 6-20). Ten patients (40%) had disease progression. In general, toxicity with LDMTX was mild. The most frequent toxic effect was stomatitis. Twelve of 14 patients who crossed over to HDMTX were evaluated for response. Six patients had stable disease and six had disease progression. We conclude that the results achieved with LDMTX seem inferior to the results achieved with HDMTX described in the literature.
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PMID:Phase II study of low-dose methotrexate in advanced osteosarcoma followed by escalation after disease progression: a study of the Soft Tissue and Bone Sarcoma Group of the European Organization for Research on Treatment of Cancer. 345 32

Thirteen patients with esophageal or gastroesophageal tumors with regional disease only were treated with sequential combined therapy. Weeks 1 to 6 continuous (24 hours) infusion 5-fluorouracil (5-FU) 300 mg/m2/d; weeks 6 to 10 or 12 infusional 5-FU administered concomitantly with radiation to the primary tumor site using standard fractionation with a cumulative median dose of 5000 rad; range 4400 to 6900 rad. Surgery was performed in five patients. All patients were evaluable for assessing response to the initial 5-FU infusion and 11/13 patients demonstrated tumor regression. Of 12 evaluable patients subsequently receiving combined infusional 5-FU and concomitant radiation, all 12 achieved complete clinical (10) or pathologic (two) tumor regression. Two of five patients having surgical resection had no pathologic evidence of tumor. All patients had relief of dysphagia within 1 week of initiating chemotherapy. Acute complications of therapy included stomatitis (two patients); hand-foot syndrome (two patients), and subclavian vein thrombosis (two patients). Stricture requiring periodic dilation occurred in three patients, and one patient developed a tracheoesophageal fistula at 36 months. Local control was maintained in 12/13 evaluable patients. Four of 13 patients were alive and without disease at 12 to 46 months. Nine patients died of distant metastases at 6 to 40 months. Median survival for the whole group was 16 months. Ten of the 13 patients (77%) survived for more than 1 year and 3/13 (22%) survived more than 3 years. This pilot study demonstrates the activity of 5-FU administered on an infusion schedule in both squamous and adenocarcinoma of the esophagus and the capacity to deliver infusional 5-FU throughout standard fractionation radiation. The local control and survival data may provide a basis for expanded Phase II trials, and a comparative trial against surgery alone might also be justified.
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PMID:Sequential infusional 5-fluorouracil followed by concomitant radiation for tumors of the esophagus and gastroesophageal junction. 359 64

We conducted parallel phase II trials of cimetidine as a single agent and the combination N-phosphonacetyl-L-aspartate (PALA) plus L-alanosine among 40 previously untreated patients with biopsy-proven, measurable disseminated malignant melanoma. We did not design the trial to be a comparative assessment of the two regimens. Among 19 patients treated with cimetidine, 300 mg orally four times daily, there was one complete response of extensive pleural and pulmonary metastases for 16+ months and two partial regressions of soft tissue lesions for 7 and 21+ months, respectively. Among 21 patients treated with the combination regimen, there was only one partial response in soft tissue for 1 month. The median times to progression and death were 1.4 and 6 months, respectively, for cimetidine, and 1.3 and 4 months, respectively, from the combination of PALA plus L-alanosine. Among patients who progressed on initial treatment, there were no responses in 12 who received crossover therapy with cimetidine and 11 with the combination regimen. Two patients treated with the combination program had severe stomatitis, two developed renal failure, and one had severe leukopenia and thrombocytopenia. Recognizing the limitations of small sample size, these early observations suggest that cimetidine may have intriguing implications in the management of disseminated malignant melanoma.
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PMID:Phase II studies of single-agent cimetidine and the combination N-phosphonacetyl-L-aspartate (NSC-224131) plus L-alanosine (NSC-153353) in advanced malignant melanoma. 359 11

Mitoxantrone (Novantrone; dihydroxyanthracenedione) is an anthraquinone previously shown to be active in human breast cancer. It appears to have less toxicity than doxorubicin. Results of this phase II-III randomized cross-over trial to determine the relative efficacy and toxicity of mitoxantrone in comparison to doxorubicin, are presented. Patients with measurable, recurrent breast cancer with limited prior chemotherapy with or without radiotherapy for metastatic disease, and who had not been exposed to prior doxorubicin, were randomized to receive either mitoxantrone or doxorubicin every three weeks with cross-over on progression. Response rates, duration of remission, time to treatment failure, and drug toxicity, including cardiac toxicity evaluated with serial radionuclide angiocardiography, were evaluated. Differences in the response rates for the two groups were not statistically significant. Neither time to treatment failure nor duration of response are significantly different (p greater than 0.05). With respect to toxicity, mitoxantrone treated patients consistently exhibited a lower incidence and less severe drug toxicity as compared to their doxorubicin-treated counterparts. Cardiac toxicity was carefully monitored and thus four patients on doxorubicin have had drug related congestive heart failure, as compared to none on mitoxantrone. In summary, mitoxantrone appears to be as active as doxorubicin in patients with stage IV breast cancer previously treated with chemotherapy; however, mitoxantrone causes significantly less nausea, vomiting, stomatitis and alopecia at doses which induce equal or greater myelosuppression than doxorubicin, and appears to be less cardiotoxic.
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PMID:A randomized trial comparing mitoxantrone with doxorubicin in patients with stage IV breast cancer. 389 78

We have treated 15 patients with advanced gastrointestinal carcinoma with a cyclical regimen of combined Ftorafur (N1-((2-furanidyl-))-5-Fluorouracil, a 5-FU pro-drug) and external beam radiation. The Ftorafur (FT) was administered orally in daily doses of between 1.0 and 2.5 g/m2/day in 3 divided doses in a Phase I format. The drug was given daily for 5 days along with conventional X ray treatment portals and daily radiation doses of 250 rad on each of the first 4 days of each treatment cycle. The patients were then rested for a minimum of 10 days or until all significant side effects had passed. The total number of 1,000 rad cycles and radiation dose were dictated by tolerance and by normal organ dose limitations. The most common toxicity in general, and the most common limiting toxicity was nausea and vomiting, in contrast to oral FT alone where diarrhea is more prominent. Stomatitis was seen only once and no other form of serious toxicity was encountered. Two-thirds of the patients responded in subjective terms (pain relief). There was 1 partial response to FT alone (pulmonary metastases outside the treatment field). The sole patient whose treatment field was outside the abdomen (chest portals for esophageal carcinoma) developed pneumonitis which contributed to his death. No other delayed effects were noted. Serum FT levels were related to the ingested dose and in the microgram range while serum 5-FU levels were in the nanogram range indicating slow decomposition of FT into 5-FU. The therapy was reasonably well tolerated at doses of 2.0 g/m2/day or lower with abdominal radiation. FT offers the potential for replacing intra-venous infused 5-FU as a clinical radiosensitizer.
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PMID:Phase I and pharmacologic study of oral ftorafur and X ray therapy in advanced gastrointestinal cancer. 391 71

Fourteen patients with advanced renal carcinoma were treated with Adriamycin 40 mg/m2 I.V., bleomycin 15 U/m2 I.V., vincristine 2 mg I.V., cyclophosphamide 200 mg/m2 p.o. x 4 days, and BCG by scarification every 4 weeks. Of 13 evaluable patients, three (23%) achieved partial remissions on therapy, five (39%) were improved, and three were stable. Responding disease sites included lung and pleural metastases, and an abdominal mass. Median duration of response was 4 months. Median survival was 8.5 months, but the partial responders survived for 13, 17, and 19 months. Toxicity included nausea and vomiting (31%), leukopenia (8%), thrombocytopenia (8%), diarrhea (15%), alopecia (8%), stomatitis (8%), and paresthesias (8%). This well-tolerated stomatitis (8%), and paresthesias (8%). This well-tolerated chemoimmunotherapy regimen has moderate activity in renal carcinoma and deserves further evaluation.
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PMID:Combination chemoimmunotherapy for advanced renal carcinoma with Adriamycin, bleomycin, vincristine, cyclophosphamide, plus BCG. 616 7

This study was designed as a Phase II clinical trial in advanced recurrent or metastatic squamous cell carcinoma of the cervix with a combination of bleomycin (B: 10 u/m2/d) and cisplatin (P: 20 mg/m2/d) administered for five consecutive days in intravenous infusion for 7 hours and vincristine (V: 1 mg/m2) and methotrexate (M: 40 mg/m2) administered only on day one of each cycle which was repeated every 28 days up to a maximum of 6 times. Over a period of 2 years, 15 evaluable patients with measurable disease received at least 3 courses of therapy. Six had recurrent disease and nine had distant metastases. All had previous radiation therapy. There were two dropouts after the first course due to nausea and vomiting which was practically universal. Other side effects included: mild paresthesias of the extremities (89%), stomatitis (41%), diarrhea (17%), moderate pancytopenia and hypomagnesemia which was reduced from 65% to 17% when magnesium sulfate 10% was administered with cisplatin. Sixty-six percent of the evaluable patients achieved remission (7 partial and 3 complete) usually before the fourth course of therapy. The disease-free interval was of 29.7 +/- 15 weeks in all responders (40.6 +/- 15.5 weeks in complete responders). The mean survival from the start of BPVM therapy was of 55.8 +/- 33.3 weeks in responders and of only 14 +/- 2.9 weeks in nonresponders (P less than 0.01). It is concluded that BPVM is an effective combination chemotherapy in advanced squamous cell carcinoma of the cervix. These results should be confirmed in a Phase III trial.
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PMID:Effective chemotherapy for advanced carcinoma of the cervix with bleomycin, cisplatin, vincristine, and methotrexate. 619 75

A Phase I trial of tricyclic nucleoside phosphate (1,4,5,6,8-pentaazaacenaphthylene-3-amino-1, 5-dihydro-5-methyl-1-beta-D-ribofuranosyl 5'-phosphate ester; NSC 280594) was conducted using a 5-day continuous infusion schedule. Thirty-seven patients with advanced cancer were entered on the study, of whom 33 patients were evaluable for response and toxicity. Dose levels ranged from 10 mg/sq m/day X 5 days to 40 mg/sq m/day X 5 days. Initially, courses were repeated every 3 to 4 weeks. As cumulative toxicity became manifested, the interval between courses was changed to every 6 weeks. Major toxicities included hyperglycemia, hepatotoxicity, and thrombocytopenia. Patients with a prior history of diabetes mellitus, extensive radiation therapy, or significant liver metastases were prone to severe toxicity. Other toxicities noted were nausea and vomiting, abdominal discomfort, anemia, and reduction in serum calcium, phosphorus, and albumin levels. Rare side effects included hypertriglyceridemia, hyperamylasemia, diarrhea, and stomatitis. Antitumor activity observed include improvement in s.c. metastases in a patient with papillary thyroid carcinoma, stabilization of disease in a patient with mesothelioma, and mixed responses in three patients (colon cancer, sarcoma, and tonsillar squamous cell cancer). Recommended schedule for Phase II studies is 20 mg/sq m/day for 5 days every 6 weeks.
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PMID:Phase I study of tricyclic nucleoside phosphate using a five-day continuous infusion schedule. 674 83

The delivery of high-dose epirubicin in patients with advanced breast cancer usually entails serious myelotoxicity and frequent treatment delays. Concurrent administration of G-CSF probably allows the administration of epirubicin on schedule with minimal morbidity. From August 1990 to February 1992, 42 women with advanced breast cancer were treated with six cycles of epirubicin 110 mg/m2 every 4 weeks. Filgrastim 5 micrograms/kg per day for 14 days was administered subcutaneously starting 24 hours after chemotherapy. All patients had multiple metastatic sites, and 39 had visceral metastases. All cases were evaluable for response, toxicity, and survival. Treatment was delayed in only two cases. The actually administered average dose per unit time per patient amounted to 99.6% of the dose prescribed by the protocol. Two (4.5%; 95% confidence interval [C.I.] 0-16%) patients demonstrated a complete response and 14 (33%; 95% C.I. 19-49%) a partial response. Median time to progression was 31 weeks and median survival was 60 weeks. Severe granulocytopenia was seen in six patients; stomatitis and diarrhea in one patient each. Myoskeletal pain was noticed in 23 (55%) patients, while cardiac problems were reported in 3 cases. The present study shows that the prophylactic use of r-met-hu G-CSF allows the administration of high-dose epirubicin every 4 weeks with minimal morbidity and an improved quality of life.
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PMID:High-dose epirubicin and r-met-hu G-CSF (filgrastim) in the treatment of patients with advanced breast cancer: A Hellenic Cooperative Oncology Group study. 752 43

Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) 250 mg/m2 by 24-hour infusion at 21-day intervals was evaluated at M.D. Anderson Cancer Center as a single agent in patients who had received one prior chemotherapy regimen either as adjuvant therapy or for metastatic disease. Of 25 patients treated, 12% had a complete remission and 44% had a partial response. The median time to progression was 9 months (range, 1 to 20 months). In the next phase of development, a phase I trial evaluated sequentially administered paclitaxel and doxorubicin as initial therapy for metastatic disease. Granulocyte colony-stimulating factor also was administered in each cycle. The dose-limiting toxicity was either stomatitis or neutropenic fever. The maximum tolerated dose (MTD) was 125 mg/m2 for paclitaxel and 48 mg/m2 for doxorubicin. Because of much lower than anticipated MTDs of both drugs in this schedule, it was hypothesized that there may be a schedule-dependent toxicity; therefore, in the second phase I study the schedule of administration was reversed (ie, doxorubicin followed by paclitaxel infusion). The MTDs of this schedule were 60 mg/m2 and 150 mg/m2 for doxorubicin and paclitaxel, respectively. Pharmacokinetic studies subsequently have confirmed that administration of paclitaxel before doxorubicin impairs the elimination of doxorubicin by some unknown mechanism. In an ongoing phase II study, paclitaxel is being evaluated in patients who have received three or more treatments with chemotherapy. Paclitaxel is administered at doses of 135 and 150 mg/m2 (for poor- and good-risk patients, respectively) without granulocyte colony-stimulating factor. Six patients (19%) have shown objective partial responses. Our initial phase II study showed significant antitumor activity for paclitaxel in patients who had received limited prior chemotherapy. Our phase I studies established that initial administration of paclitaxel alters the pharmacokinetics of doxorubicin and increases morbidity. The reverse sequence of administration was associated with better tolerance and a higher MTD. In heavily treated patients this drug also has significant antitumor activity.
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PMID:Paclitaxel in the treatment of metastatic breast cancer: M.D. Anderson Cancer Center experience. 754 Nov 51


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