Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thirty-two patients with primary osteosarcoma and 18 patients with advanced osteosarcoma were treated by iv or ia infusion of cisplatinum at a dose of 100 mg/m2 every three weeks. The efficacy of the agent for primary osteosarcoma was mainly estimated by X-ray findings and histologic examination. One patient had a partial response, and 7 patients had a minor response. Pathologic evaluation of the extent of the primary tumor necrosis was performed on 27 resected specimens. Eight of 27 cases showed a good response (Ayala III A less than). One of 18 patients with advanced osteosarcoma had a partial response, and 2 a minor response. Nausea and vomiting (88%), liver dysfunction (42%), leukopenia (36%), nephrotoxicity (20%) and auditory disturbance (20%) were the main side effects in 50 patients. However, side effects of cisplatinum were generally reversible. The results suggest that cisplatinum is effective against osteosarcoma and may enhance the therapeutic results in osteosarcoma.
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PMID:[Cis-dichlorodiammineplatinum in osteosarcoma. Osteosarcoma Cooperative Study Group report]. 265 22

A total of 20 children with recurrent or unresponsive tumours (10 Wilms' tumours, 3 rhabdomyosarcomas, 4 Ewing's sarcomas, 1 osteosarcoma, 1 hepatoblastoma, 1 hepatoma) were given ifosfamide as a 24-h infusion (5 g/m2), with mesna as a uroprotector. The number of courses ranged from 1 to 13 (median, 3), and the interval between them was 2-3 weeks. In all, 16 of these patients had previously received cyclophosphamide. Complete clinical responses (CRs) were seen in 3 cases (2 Wilms' tumours and 1 Ewing's sarcoma) and lasted 5, 7, and 9 months. Partial responses (PRs) were seen in 3 instances; mixed response or stable disease, in 4; and progressive disease, in 10. Treatment was well tolerated in most patients, with no cystitis or severe myelosuppression, but two children developed transient neurological symptoms and one became hypertensive. Nausea and vomiting were controlled by high-dose dexamethasone in most children.
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PMID:A phase II study of ifosfamide in paediatric solid tumours. 275 66

Ifosfamide was given to 61 patients with malignant solid tumors diagnosed before the age of 21 years. In this phase II study, all patients received 1.6 g/m2/day X 5 iv over 15 minutes followed by mesna at a dose of 400 mg/m2 iv at 15 minutes and 4 and 6 hours after ifosfamide. Responses were observed in five of 15 patients with osteosarcoma, two of ten with neuroblastoma, two of six with Wilms' tumor, two of five with rhabdomyosarcoma, four of eight with other soft tissue sarcomas, one of one with retinoblastoma, one of two with germ cell tumors, one of one with B-cell lymphoma, and one of one with a primitive neuroectodermal tumor. Fifty-nine of 61 patients had received prior alkylating agent therapy which included cyclophosphamide, cisplatin, mechlorethamine, melphalan, or dacarbazine. Fourteen of 19 responses developed in patients whose tumors were resistant to treatment with cyclophosphamide. A patient with malignant Schwannoma who had received no prior chemotherapy developed a complete response which lasted 12 months. A patient with brain metastases of osteosarcoma has had complete response for greater than 2 years. Complete response was also observed in a patient with B-cell lymphoma. Toxicity consisted of mild to moderate nausea and vomiting, transient reversible myelosuppression, occasional elevation of serum BUN or creatinine, and transient neurotoxicity characterized by somnolence, confusion, weakness, tremor, hallucinations, or seizures. We conclude that ifosfamide is an important alkylating agent without apparent complete cross-resistance with cyclophosphamide, and as such should be further investigated for determination of its activity in patients with pediatric neoplasms and considered for incorporation into phase II-III trials for certain tumors.
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PMID:Phase II trial of ifosfamide in children with malignant solid tumors. 310 34

One hundred twenty-four children and young adults with recurrent tumors, predominantly sarcomas, were treated with the combination of ifosfamide, etoposide, and the uroprotector, mesna (2-mercaptoethane sulphonate), in a phase II trial. The treatment regimen consisted of 12 cycles of therapy administered every 3 weeks. After evaluation of the tumor response to chemotherapy alone, radiation or surgery was used to eradicate residual sites of metastatic disease where possible. At the present time, 77 patients are evaluable for response to the chemotherapy; 43 of the patients have experienced a significant reduction in the tumor size in response to the chemotherapy alone (39 partial responses [PR] and four complete responses [CR]). Sixteen of 17 patients with Ewing's sarcoma, nine of 13 with rhabdomyosarcoma, four of eight with peripheral neuroepithelioma, three of eight with osteosarcoma, and 11 of 31 with other tumors have responded with a PR or CR. The toxicity of the regimen was acceptable. Moderate or severe toxicity evaluated on a per cycle basis included: neutropenia, 97%; thrombocytopenia, 32%; nephrotoxicity, less than 1%; mucositis, 1%; neurologic toxicity, 2%; nausea and vomiting, 13%; hemorrhagic cystitis, less than 1%. Fever was present after 33% of cycles and sepsis following 7%. One patient died due to sepsis and pancytopenia. At the present time, only seven of the 43 patients who responded to the chemotherapy regimen have relapsed, with a median follow-up of 10 weeks after the response. This drug combination is highly active in the treatment of recurrent sarcomas and other tumors in children and young adults.
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PMID:Ifosfamide with mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. 311 35

Four patients with osteosarcoma were treated with intensive chemotherapy and autologous bone marrow transplantation (ABMT). The patients received high-dose methotrexate (9-12 mg/m2) with citrovorum factor rescue, high-dose melphalan (60 mg/m2 X 3), actinomycin D (0.5 mg/m2 X 3), adriamycin (30 mg/m2 X 2) and high-dose cyclophosphamide (60 mg/kg X 2) during 4 weeks. Bone marrow was aspirated and cryopreserved before treatment and reinfused 48 hours after the completion of chemotherapy. Two of four patients had advanced osteosarcoma with multiple pulmonary metastasis, one of whom had responded well and achieved partial response while the other had shown no response, and both patients died of disease progression 4 and 11 months after ABMT, respectively. The other two patients who received this regimen at an earlier disease stage for prevention of pulmonary metastasis, are alive and well without any evidence of metastasis 31 and 18 months after ABMT, respectively. This regimen was tolerated well in all patients except for mild nausea and vomiting. No infectious episodes were observed during the period of aplasia which continued for 19 to 38 days after marrow infusion. These results suggest that this supralethal combination chemotherapy is safe and tolerable when used with ABMT and effective for patients with osteosarcoma, especially when applied in the non-metastatic phase.
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PMID:[Autologous bone marrow transplantation in osteosarcoma]. 329 55

The effectiveness of cis-diammine-dichloroplatinum (cisplatinum, platidiam, DDP) alone or as a component of combined treatment was evaluated in 85 patients with osteogenic sarcoma. The said drugs were used as adjuvants following radical surgery (group I-18 cases), in combined treatment of solitary and single lung metastases (group 2-7 cases) and in 60 patients with advanced tumors (group 3). An analysis of long-term results showed response in 30.8% in group 3. In group 2, application of chemotherapy plus surgery was followed by remissions of 2-46+-month duration (mean-13.9 months). In group I, 78.7% are expected to survive metastasis-free more than 12 months. Toxicity was moderate, with nausea and vomiting (87.1%), myelosuppression (52.8%), nephrotoxicity (48.6%) and alopecia (75.7%) being the most common side-effects.
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PMID:[Experience with and outlook for the use of cisplatin in the combined therapy of osteogenic sarcoma]. 347 57

A phase I study of carboplatin (CBDCA) was performed in 40 children with advanced cancer. A single course of CBDCA consisted of 4 weekly 1-hour infusions followed by a 2-week rest. The starting dose of 100 mg/m2/week was 66% of the maximum tolerated dose in adults. Escalated dose levels given were: 125, 150, 175, and 210 mg/m2. Myelosuppression was dose limiting, with thrombocytopenia more pronounced than leukopenia. There was no evidence of cumulative toxicity. The maximum tolerated dose for children with solid tumors was 210 mg/m2/week X 4. Other side effects included transient nausea and vomiting at the higher dose levels and non-dose-related, reversible changes in creatinine clearance. One patient developed hives. No hepatic toxicity was seen. Among the 28 evaluable patients with solid tumors, one of ten with osteogenic sarcoma had complete disappearance of a lung nodule for 15+ months. Two of four patients with medulloblastoma had partial responses by clinical and computerized tomographic scan for 4 and 10 months. All three responders had received prior cisplatin therapy. CBDCA has major advantages over cisplatin in terms of reduced toxicity. Responses observed in patients previously treated with cisplatin are encouraging. The recommended phase II dose for children with solid tumors is 175 mg/m2/week X 4 with a 2-week rest.
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PMID:Phase I study of carboplatin (CBDCA) in children with cancer. 352 46

Carboplatin has been developed for clinical trials as a less nephrotoxic, less emetogenic analog of cisplatin. In preclinical tumor models it was less potent than the parent compound on a molar basis, but reduced toxicity allowed comparable antitumor doses to be given. In phase I studies its dose-limiting toxicities were reversible myelosuppression, especially thrombocytopenia. Leucopenia and anemia occurred to a lesser degree. Other reported toxicities included nausea, vomiting, malaise, myalgia, arthralgia, ototoxicity, hypomagnesemia, and proteinuria. Nausea and vomiting occurred frequently, but was much less severe than that observed with cisplatin. The incidence of serum creatinine elevations was low. The increase was usually reversible and occurred only in association with administration of aminoglycosides, or abnormal pretreatment renal function. Recommended phase II doses by schedule are: bolus every 4 weeks, 400-500 mg/m2 (560 mg/m2 in children); 24 hour continuous infusion every 4 weeks, 320-400 mg/m2; weekly bolus for 4 consecutive weeks with 2 weeks rest, 100-125 mg/m2 (175 mg/m2 in children); bolus for 5 consecutive days every 4 weeks, 77-95 mg/m2. Objective responses were observed during these phase I studies in adult patients (head and neck, breast, renal carcinomas) and children (osteosarcoma, brain stem lesions). In addition to phase II evaluations in all major tumor types, plans for phase III studies in selected tumors are underway.
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PMID:Results of NCI-sponsored phase I trials with carboplatin. 391 Feb 21

Ifosfamide given to 42 patients iv at 2-2.5 g/m2/day X 4 resulted in partial responses in ten of 28 (36%) evaluable patients with adult soft tissue sarcomas, including two of two with chondrosarcoma; none of nine with pediatric sarcomas (Ewing's sarcoma, osteogenic sarcoma, or rhabdomyosarcoma) achieved partial response. All of the pediatric patients had failed to respond to complicated three- to six-drug regimens of up to 18 months in duration. The response rates in patients with and without prior cyclophosphamide (32%; seven responses among 22 patients; and 20%, three responses among 15 patients) were not significantly different, supporting in vitro evidence of a lack of cross-resistance between the two related compounds. Myelosuppression was dose-limiting. Hemorrhagic cystitis was not observed in patients treated with 400-500 mg of mesna iv every 4 hours during ifosfamide treatment. Nausea and vomiting were generally mild or moderate. Alopecia was universal but reversible. Of the first 11 patients, five became somnolent or developed visual hallucinations (during six of the 12 total courses administered to the five patients). Only one patient had two episodes of neurotoxicity. After reduction of the use of iv antiemetics and major narcotics, single episodes of neurotoxicity were seen in five of the next 27 patients. An asymptomatic acidosis developed in most patients, requiring bicarbonate replacement in one. Ifosfamide appears to be active in previously treated patients with sarcomas and should be evaluated in patients with less extensive prior treatment.
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PMID:Phase II trial of ifosfamide with mesna in previously treated metastatic sarcoma. 392 1

Twenty children with recurrent or unresponsive tumours (10 Wilms', 3 rhabdomyosarcoma, 4 Ewings's, 1 osteosarcoma, 1 hepatoblastoma, 1 hepatoma) and one untreated patient with renal carcinoma were given ifosfamide as a 24-h infusion (5 mg/m2), with mesna as uroprotective. The number of courses ranged from 1 to 13 (median 3), and the interval between them was 2-3 weeks. Sixteen of these patients had previously received cyclophosphamide. Complete clinical responses were seen in 3 cases (2 Wilms' and 1 Ewing's) and lasted 5, 7, and 9 months. Partial responses were seen in 3 instances, mixed response or stable disease in 4, and progressive disease in 11. Treatment was well tolerated in most patients, with no cystitis or severe myelosuppression, but 2 children developed transient neurological symptoms and 1 became hypertensive. Nausea and vomiting were controlled by high-dose dexamethasone in most children. Plasma ifosfamide levels were estimated by means of gas-liquid chromatography in 10 patients. Peak concentrations ranged from 38 to 125 micrograms/ml (median 80). The elimination half-life, at 2.5-5.2 h (median 3.2) was shorter than previously reported in adults. Future studies should test the possibility that ifosfamide-containing combination chemotherapy may be more effective than the regimens, usually including cyclophosphamide, that are currently used as front-line treatment of embryonal and Ewing's sarcoma.
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PMID:A phase II study of ifosfamide in children with recurrent solid tumours. 405 69


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