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 53-year-old woman with recurrent ovarian cancer sustained an intracerebral hemorrhage after the 4th course of a chemotherapy regimen which included cis-platinum (DDP). She received high-dose methylprednisolone as an antiemetic along with the DDP. No metastases or abnormal vascularity were found on histological examination of the right frontal lobe which had been removed surgically. Causes of cerebrovascular accidents during and following chemotherapy are discussed.
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PMID:Acute cerebrovascular accident after treatment with cis-platinum and methylprednisolone. 668 45

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

Cisplatin (DDP) is an active agent in the treatment of disseminated bladder cancer. In addition to its direct tumor cytotoxicity, recent animal and clinical data suggest synergism with radiation therapy (RT). Since improved survival with preoperative RT is largely restricted to bladder cancer patients in whom radiation-induced downstaging (P less than T) may be recognized, the authors administered DDP + RT preoperatively to patients with locally advanced (T3, T4) bladder tumors selected for cystectomy. The aim was to evaluate the feasibility of such a combination in relation to surgical and hematologic complications, the immediate effect on tumor downstaging, disease progression, and survival. Two thousand rad (400 rad X 5 days) was delivered to the whole pelvis, followed by cystectomy in 2 days. DDP (70 mg/m2) was given intravenously on day 2 of the RT. Twenty-four patients received preoperative DDP + RT and underwent attempted cystectomy; however, six patients were nonresectable owing to extensive pelvic disease, and an additional five patients had resectable pelvic lymph node metastases. Pelvic complications developed in 3 of 24 (12%) patients, but none required reoperation. No patient had a wound dehiscence. Transient myelosuppression was similar to that induced by 2000 rad preoperative RT alone. Tumor downstaging (P less than T) was seen in 9 of 24 (38%) patients, and in 5 (21%) patients, no tumor was found in the surgical specimen (P0). Distant metastases alone have been detected in 4 of 18 (22%) patients who had a cystectomy (all 4 had nodal metastases). Disease-free survival at a median follow-up of 22 months (range, 12-34 months) is 60% (14/24) for all patients (89% for P less than T and 40% for P greater than or equal to T patients) and 78% (14/18) for the resected patients. Combined preoperative DDP + RT proved to be a safe and feasible regimen which resulted in a possibly greater recognition of radioresponsive bladder tumors, and after cystectomy, an encouraging early survival rate in patients with locally advanced disease.
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PMID:Planned preoperative cisplatin and radiation therapy for locally advanced bladder cancer. 668 67

Eighteen evaluable patients with squamous cancer of the uterine cervix recurrent after radiation therapy or with distant metastases were treated with dianhydrogalactitol (150 mg/m2) and cisplatin (DDP) (50 mg/m2), both given iv every 3 weeks. Only 39% of the patients responded, a result no better than that previously reported for DDP alone and only one-half as good as that previously reported by our group for a combination of this drug with mitomycin, vincristine, and bleomycin. Responses lasted a median of only 5 months. Hematologic toxicity was life-threatening in 22% of the patients and was severe in all but 11% of the remaining patients. We conclude that the addition of substantial and toxic doses of dianhydrogalactitol to DDP failed to substantially enhance the rate, quality, or duration of response compared to DDP alone.
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PMID:Dianhydrogalactitol and cisplatin in combination for advanced cancer of the uterine cervix. 688 13

The antimetastatic effects of two drugs, cis-diamminedichloroplatinum(II) (DDP) and hydrocortisone (liposome-incorporated or free), were studied. The experimental models were regional and distant metastases of hepatoma A and pulmonary adenocarcinoma, which were transplanted into the footpads of A/He mice. Liposomes were prepared from phosphatidylcholine by sonic dispersion. DDP and hydrocortisone were injected sc into the region of the plantar aponeurosis of the foot with the primary tumor. This administration route was considered to be equivalent to the intralymphatic route. Evidence indicated that only liposome-incorporated DDP and hydrocortisone decreased significantly the frequency and growth rate of tumor metastases in the regional lymph nodes. The effect observed was not due to the direct action of the drugs on the primary tumors. When nonencapsulated, these drugs were ineffective. Both liposome-encapsulated and free DDP did not affect distant metastases of pulmonary adenocarcinoma. The intralymphatic administration of liposome-encapsulated antitumor agents is suggested as a method for the prophylactic treatment of tumor metastases in the lymph nodes.
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PMID:Intralymphatic administration of liposome-encapsulated drugs to mice: possibility for suppression of the growth of tumor metastases in the lymph nodes. 693 32

Methotrexate (MTX) in high doses (3 to 7.5 g/m2) with leucovorin rescue (HDMTX-LCV) can be delivered on a weekly basis in a setting of proper pharmacologic monitoring. Myelosuppression occurs in 28 per cent of the patients and in 8 per cent of the courses and usually results from delayed MTX excretion secondary to mild reversible nephrotoxicity. The incidence of tumor regression was 50 per cent in head and neck cancer; 59 per cent in non-Hodgkin's lymphoma; 40 per cent in small cell lung cancer; 24 to 50 per cent in breast cancer and 50 per cent in osteogenic carcinoma, for an over-all response rate of 39 per cent (70 of 178) in patients with disseminated cancer. HDMTX-LCV is not recommended for the conventional treatment of metastatic cancer because of the potential for toxicity and the fact that the response rates cited are probably not superior to those which can be achieved by conventional doses of MTX. However, the relative lack of myelosuppression and mucositis, when compared to conventional unrescued MTS, and the achievement of therapeutic concentrations of MTX in the central nervous system with the HDMTX-LCV program have led to its incorporation into clinical trials of combination chemotherapy.
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PMID:High dose methotrexate with leucovorin rescue. Rationale and spectrum of antitumor activity. 696 19

From December 1973 to november 1978, 31 patients with osteosarcoma were treated with combination chemotherapy consisting of cyclophosphamide, vincristine, adriamycin and DTIC. 11 out of 19 patients with localized osteosarcoma are alive with no evidence of disease, 14+ to 40+ months after initiation of adjuvant postoperative chemotherapy. The probability of relapse-free survival for this group was calculated as 62% at 2 years and 48% at 3 years. Considering the 15 patients with osteosarcoma of the limbs relapse-free survival will be 79% at 2 years and 62% at 3 years. In 10 of 11 patients with no relapse the primary tumor has been located in the metaphysis of the proximal tibia or the distal femur. All patients with osteosarcoma of the trunk have died from metastases. Most of the 12 patients with metastasizing osteosarcoma died within one year after onset of chemotherapy. In none of these patients a complete remission could be achieved. For patients receiving adjuvant chemotherapy results are comparable with those reported by other investigators. In patients with disseminated osteosarcoma alternative chemotherapy regimens including adriamycin, cis-dichloro-diammine-platinum and ifosfamide may prove superior. In a pilot-study using vincristine-adriamycin-DDP or ifosfamide-DDP response to chemotherapy was noted in 4 out of 7 patients with two continuing complete remissions for 13+ and 5 1/2+ months, respectively.
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PMID:[Results of cytostatic therapy with cyclophosphamide, vincristine, adriamycin and DTIC (CYVADIC) in localized and metastasized osteosarcoma. A retrospective analysis]. 699 10

The authors report the results of a trial of the treatment of recurrences of advanced carcinomas of the bladder using Cis-Diamino-Dichloro-Platinum administered by continuous IV infusion over a period of 24 hours at a dose of 100 mg/m2, under cover of hyperhydration and anti-haematizing drugs. The trial involved 10 patients who has had the following initial treatment : - excision for 8 of them (2 total cystectomies for T4, one total cystectomy for T3B, 2 total cystectomies for T3A and 3 partial cystectomy for T1); - preoperative cobalt therapy for 7 of them (2 flashes of 7.5 gray) - postoperative chemotherapy (VM26 and 5FU) for 5 patients. The targets evaluated were : 7 remaining pelvic tumours or recurrences, 3 lung metastases, two cases of venous compression with oedema of the lower limbs, 3 node metastases, 3 bone and 1 sciatic metastases. Results : - 1 complete remission with disappearance for 10 months in the same patient of pulmonary metastases, venous compression and an inguinal node; - 3 partial remissions for 2 to 9 months; - 2 minor remissions of 3 to 5 months; - 3 stabilizations and 1 progression. It is interesting to note the greater efficacy on distant metastases (2/3 complete disappearances of lung metastases, 2/2 disappearances of oedema of the lower limbs) than on pelvic tumours (4/7 regressions). In total, 4 objective responses out of 10 occurring between the 2nd and 6th week after the first course. The authors announce a valuable synergism of DDP with cyclophosphamide and adriamycin.
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PMID:[Evaluation of the efficacy of cis-diamino-dichloro-platinum as monochemotherapy in the treatment of advanced malignant tumours of the bladder (author's transl)]. 719 29

This review covers the clinical significance of neoadjuvant chemotherapy as initial treatment for squamous cell carcinoma of the head and neck, especially focusing on advanced but resectable disease. The rates of complete response (CR) after chemotherapy depended on the regimens and varied from 15% to 35%. Combined use with DDP/5-FU was considered as a most effective regimen. In addition of leucovorin to DDP/5-FU regimen, CR rate increased more than 50%. A randomized clinical trial has not shown any advantage for survival in advanced head and neck cancer. Recent reports have shown that distant metastases diminished in patients treated with neoadjuvant chemotherapy. When primary lesions disappeared completely after neoadjuvant chemotherapy, sequential use of radiotherapy can make the long term relapse-free in those lesions. This effort may lead to a modality of cancer treatment without surgery, so organ preservation will be possible.
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PMID:[Role of neoadjuvant chemotherapy for management of resectable head and neck cancer]. 812 81

This investigation was to establish a clinically relevant experimental model to evaluate the pharmacodynamics of drugs used for head and neck cancers. A total of 83 surgical samples of primary and lymph nodal metastatic tumors was obtained from 66 patients. Fragments of these tumors were cultured on a collagen gel matrix. The tumor cell labeling index (LI) was determined by [3H]thymidine incorporation and autoradiography. Seventeen tumors (20%) were contaminated. About 80% of the remaining 65 tumors were successfully cultured for at least 2 weeks. The cultured tumor fragments retained the morphology and architecture of the freshly removed specimens; both tumor and stromal cells were present. The tumor cell LI after 2-3 weeks in culture, determined from the most proliferative area of the tissue, averaged 77 +/- 12% for primary tumors and 78 +/- 12% for nodal metastases. The activity of three clinically active agents, 5-fluorouracil (FU), cisplatin (DDP), and mitomycin C (MMC), was evaluated in 47 tumors. All three drugs inhibited the tumor LI. The concentrations needed to produce a 50% inhibition of the tumor LI (IC50) were within the clinically achievable concentration range. The intertumor variation in the IC50 for FU (60-fold) was considerably greater than that for DDP and MMC (7- to 8-fold). The nodal metastatic tumors appeared to be less sensitive to FU than the primary tumors, while there were no apparent differences for DDP or MMC.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Histocultures of patient head and neck tumors for pharmacodynamics studies. 827 13


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