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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Between July 1986 and February 1991, 10 patients with small cell carcinoma of the cervix were prospectively treated with combination chemotherapy using cisplatin (50 mg/m2) and doxorubicin (50 mg/m2) on Day 1 and etoposide (75 mg/m2) on Days 1-3. All patients underwent an extensive pretreatment metastatic survey and had histologic confirmation of small cell carcinoma prior to entry in the study. Seven patients had stage Ib, 1 stage IIa, and 2 stage IIb. Nine patients received chemotherapy at primary presentation and 1 was treated for recurrent disease. In 6 cases, chemotherapy was given and then followed by radiation therapy. Three patients received chemotherapy following radical hysterectomy and 1 was treated for persistent disease after radiation therapy. Patients received a median of four courses of chemotherapy (range 2-6). Neutropenia was the dose-limiting toxicity with 9 of 10 patients requiring a dose reduction. There was no instance of neutropenic sepsis or other major toxicity. Seven patients had measurable disease at the start of therapy. Three of these patients had a complete clinical response, 1 had a partial response, 2 had stable disease, and 1 had progressive disease (response rate = 57%). The median survival was 28 months. At the time of this report, 4 of 6 patients with stage Ib cancers given primary treatment on this regimen remained free of disease (with 28 months the median follow-up). Our pilot study indicates that this chemotherapy regimen has activity in small cell carcinoma of the cervix and should be further evaluated as an adjuvant to surgery or radiation in patients with early stage disease.
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PMID:Treatment of small cell carcinoma of the cervix with cisplatin, doxorubicin, and etoposide. 133 Aug 47

Neuraxis radiation therapy (RT) for primary intracranial tumors is associated with major late effects if administered to very young children. To control residual tumor and to delay RT, we treated eight young children (median age 6.5 months) with primary central nervous system (CNS) tumors using combination chemotherapy: cisplatin, 20 mg/M2/day plus VP-16, 75 mg/M2/day i.v. for 5 days, given q. 3-6 weeks for 8 cycles. The tumors were medulloblastoma (one), malignant ependymoma (two), primitive neuroectodermal tumor PNET (two), malignant glioma (two), astrocytoma (one). Six had measurable disease; three had positive cerebrospinal fluid (CSF) cytopathology. All patients with measurable tumor had initial objective responses (three) complete response [CR], one partial response [PR], two minor response [MR], including cytopathology (three CR of three) and metastatic deposits (two CR of two). One patient relapsed during chemotherapy. Median time to disease progression was 17.5 months; median survival was 34 months. Three patients, none of whom received RT, have prolonged progression-free intervals of 47-67 months to date. Neurodevelopmental progress continued during and after chemotherapy. Chemotherapy toxicity was mild. Median neutrophil nadir was 312/mm3, platelets 72,000. Fever during neutropenia occurred in six of 61 courses. Moderate high-frequency auditory losses were detected in three patients, and mild renal injury (GFR less than 70 ml/min) was detected in two of seven evaluable children. This pilot study demonstrates the apparent efficacy and mild toxicity of 5 day courses of cisplatin plus VP-16, with delayed RT, in young children with CNS neoplasms. A POG treatment protocol that incorporates cisplatin plus VP-16 is evaluating primary chemotherapy with delayed radiotherapy in larger numbers of pediatric brain tumor patients.
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PMID:Efficacy of postoperative chemotherapy using cisplatin plus etoposide in young children with brain tumors. 199 Feb 53

Both single-agent cisplatin and the combination of doxorubicin and cyclophosphamide demonstrated moderate activity against endometrial carcinoma in earlier salvage trials. Since January 1979, 102 patients with advanced primary (n = 42) or recurrent (n = 60) endometrial carcinoma were prospectively treated with cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) (PAC). PAC was administered monthly until disease progression or toxicity precluded additional therapy. Patients received a median of five treatment cycles (range 1-13). Of the 87 patients with measurable disease, 12 had a complete clinical response, while 27 had a partial clinical response, for an overall objective response rate of 45%. No differences in response rates between primary and recurrent disease patients were noted. Median time to response was 2.5 months with a median response duration of 4.8 months. Nonresponders included 33 patients with stable disease and 15 with progression. Median progression-free survival for all patients was 6 months. Dose escalation was possible in 25% of patients; however, 52% of patients required dose reductions during treatment. Clinically significant toxicities included neutropenia (65%), anemia (47%), emesis (21%), nephrotoxicity (17%), and neurotoxicity (4%). Our study indicates that endometrial cancer is significantly responsive to PAC. Enthusiasm for this regimen should be tempered by the limited duration of response and substantial treatment toxicity.
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PMID:Prospective treatment of advanced or recurrent endometrial carcinoma with cisplatin, doxorubicin, and cyclophosphamide. 201 51

Medulloblastoma, pineoblastoma, and cerebral neuroblastoma are malignant embryonal tumors of the CNS that may demonstrate similar histologic features, a propensity for neuraxis dissemination and sensitivity to radiation therapy and, in certain cases, chemotherapy. To evaluate the activity of preirradiation chemotherapy in such tumors, 11 newly diagnosed children with measurable residual disease and characteristics indicative of poor prognosis were treated postoperatively with cisplatin (CDDP) and etoposide (VP-16). Responses graded on the basis of radiographic findings in areas of either macroscopic residual tumor or metastatic disease included two complete responses (CRs), eight partial responses (PRs), and one stable disease (SD). Acute and subacute toxicity consisted of high-frequency hearing loss in four patients, reversible signs and symptoms of increased intracranial pressure in two patients, and transient neutropenia. Seven of eight patients with high-risk medulloblastoma and two of two with pineoblastoma remain free of tumor progression following neuraxis irradiation at 8 to 48 months postdiagnosis (median, 18 months). CDDP and VP-16 is a highly active drug combination when given before irradiation in children with high-risk medulloblastoma and other malignant embryonal tumors of the CNS, producing objective responses in at least one site of measurable disease in 10 of 11 newly diagnosed patients, including all of five with gross neuraxis dissemination.
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PMID:Preirradiation cisplatin and etoposide in the treatment of high-risk medulloblastoma and other malignant embryonal tumors of the central nervous system: a phase II study. 215 66

We conducted a phase II clinical trial using ifosfamide (IFX) as a single agent in cisplatin-refractory male germ cell tumor. Thirty patients with measurable disease were treated with IFX, 2 g/m2 intravenously (IV) for 5 consecutive days every 3 weeks. N-acetylcysteine, 2 g orally every 4 hours, was given as a uroprotective agent. All patients had previously been treated with cisplatin, vinblastine, and bleomycin, and all except two also had previously received etoposide. There were six partial responses (PR) and one complete response (CR) for an overall objective response rate of 23%. The median duration of response was 3.5 months (range, 2 to 5.5 months). The median survival time was 3.5 months (range, 2 to 14+ months). The toxicity of the regimen consisted of hematuria (65% of the patients), nausea and vomiting (43%), neutropenia (WBC less than 2,000; 52%), thrombocytopenia (platelet count less than 50,000; 20%), and nephrotoxicity (12%). Hematuria was dose related, occurring in 48% of courses using 2 g/m2/d v only 5% of courses at lower doses. Serious nephrotoxicity (creatinine level greater than 6.0 mg/mL) was observed in three patients with an elevated pretreatment serum creatinine level. In conclusion, IFX is an active agent in this heavily pretreated population with advanced refractory germ cell tumor.
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PMID:Ifosfamide in refractory male germ cell tumors. 351 Feb 80

Fifteen patients with metastatic mixed mesodermal sarcoma of the uterus received high dose doxorubicin infusion therapy. For 12 patients, the initial dose was 90 mg/m2; the other three patients' starting doses were 50, 75, and 75 mg/m2 respectively. Twelve patients received doxorubicin as firstline chemotherapy, with a cumulative dose of 90 mg/m2 to 675 mg/m2 (median = 495 mg/m2). Three patients treated secondarily received cumulative doses of 90, 205, and 425 mg/m2. Of nine patients who had measurable disease, none had an objective response. The median survival of the 15 patients was 11.3 months, with a range of 0.5 to 51+ months. Two patients died of neutropenia related sepsis. Cardiotoxicity occurred in two patients. Eleven patients are dead of disease, and two patients are alive without evidence of disease at 49, and 51 months. Extending the doxorubicin dosage to its tolerable limits did not appear to result in improved efficacy in patients with metastatic mixed mesodermal uterine sarcomas. Future clinical trials should concentrate on doxorubicin-containing combination regimens and Phase II single agent studies.
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PMID:High-dose doxorubicin infusion therapy for disseminated mixed mesodermal sarcoma of the uterus. 381 2

Four children with yolk sac tumor were treated with an aggressive combination chemotherapy program. Three children had presacral primary tumors, one having pulmonary metastases, and one had a testicular primary tumor with pulmonary metastases. Three children were treated when they had measurable disease, and one had no measurable disease. The chemotherapy program consisted of a 6-wk induction period with vincristine (VCR), cis-diamminedichloroplatinum (DDP), and bleomycin. Maintenance therapy consisted of VCR, actinomycin D, and cyclophosphamide (cytoxan) every 3-4 wk as tolerated. Treatment was discontinued after 12 mo of complete remission. All three patients with evaluable disease had a partial response (PR) to induction therapy. Two underwent surgical exploration following induction therapy, one a laparotomy and the other a thoracotomy, and were found to have only scar tissue at the sites of presumed residual disease. The third child with measurable disease progressed to a clinical complete response (CR) during maintenance therapy. Two patients have had no evidence of disease (NED) for 42+ and 41+ mo since starting therapy (28+ and 27+ mo since completing treatment). Two patients are NED 11+ and 7+ mo since starting therapy and remain on treatment. We have encountered no significant renal or pulmonary toxicity, and there have been only two hospitalizations during maintenance therapy for fever and neutropenia. These preliminary results employing different induction and maintenance chemotherapy programs and planned second-look surgical intervention appear encouraging.
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PMID:The use of different induction and maintenance chemotherapy regimens for the treatment of advanced yolk sac tumors. 619 71

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

Promising preclinical data and reasonable toxicity in Phase I trials encouraged the Gynecologic Oncology Group to study Fazarabine (FZB) in patients with recurrent squamous cell cancer of the cervix. Twenty-three patients with histologically proven recurrent cervical cancer with measurable disease received FZB at a dosage of 30 mg/m2 per day for 5 days; cycles repeated every 28 days. In the absence of grade 3 or 4 toxicity, dose escalation was planned to a maximum dose of 40 mg/m2 per day for 5 days. All patients were evaluable for toxicity. Seven patients developed neutropenia; in two instances, it was considered life-threatening. The only other serious adverse effect was seen in one patient who developed grade 4 nephrotoxicity. Nineteen women who had failed prior chemotherapy were evaluable for response. There were no complete or partial responses; and seven had stable disease. Fazarabine exhibits no demonstrable activity in this patient population at the dose and schedule tested and further clinical trials as second-line chemotherapy are not warranted.
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PMID:A phase II study of fazarabine (NSC 281272) in patients with advanced squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study. 757 64

A phase IIb trial using liposome-encapsulated muramyl tripeptide phosphatidylethanolamine (L-MTP-PE) in combination with ifosfamide (IFX) for patients with relapsed osteosarcoma was undertaken to determine (a) the tolerability of the combination therapy, (b) if L-MTP-PE increased the toxicity of IFX, and (c) whether IFX altered or suppressed the in vivo immune response to L-MTP-PE. Patients had histologically proven osteosarcoma and pulmonary metastases that either developed during adjuvant chemotherapy or were present at diagnosis, persisted despite chemotherapy, and recurred following surgical excision. Stratum A patients were rendered clinically free of disease within 4 weeks of study entry prior to receiving combination therapy. IFX was administered at 1.8 g/m2 for 5 days every 21 days for up to eight cycles. L-MTP-PE was administered twice weekly for 12 weeks, then once weekly for 12 weeks. Once cycle of combination therapy was defined as 5 days of IFX and 3 weeks of L-MTP-PE therapy. Stratum B patients had measurable disease at study entry that was judged to be amenable to surgical resection. Stratum B patients received three cycles of combination therapy prior to surgery to judge clinical and histologic response. Postoperatively, patients received an additional five cycles. A total of nine patients were entered into the protocol: six on stratum A and three on stratum B. Serial blood samples were collected and assayed for cytokine levels (tumor necrosis factor-alpha [TNF alpha], interleukin-6 [IL-6], IL-8, neopterin, C-reactive protein). In addition, peripheral blood monocyte tumoricidal activity was evaluated pre- and post-combination therapy. Complete blood counts with differential and platelet counts were followed weekly. No increase in the toxic side effects of IFX was demonstrated when administered with L-MTP-PE nor were delays in IFX administration due to neutropenia experienced. The toxic side effects of L-MTP-PE were also not increased. Elevations of serum C-reactive protein, plasma neopterin, IL-6, IL-8, and TNF alpha following combination therapy were similar to those observed in patients treated with L-MTP-PE alone. Monocyte-mediated tumoricidal activity was elevated 24 and 72 h following L-MTP-PE and IFX therapy, similar to what has been reported following L-MTP-PE alone. Tumor specimens obtained from stratum B patients showed the histologic characteristics consistent with a "chemotherapy effect," i.e., dead, amorphous, acellular osteoid with cell drop-out.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Combination therapy with ifosfamide and liposome-encapsulated muramyl tripeptide: tolerability, toxicity, and immune stimulation. 761 44


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