Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Prospective treatment of advanced or recurrent endometrial carcinoma with cisplatin, doxorubicin, and cyclophosphamide. 201 51

Twenty-five patients with recurrent or advanced-stage endometrial cancer were treated with cisplatin, doxorubicin, and cyclophosphamide (PAC) from May 1982 to November 1987. A retrospective chart analysis was performed to evaluate the effect of treatment on survival and progression-free interval. Toxicity was moderate. Neutropenia was the most common side effect. Age, performance status, and tumor cytoreduction were statistically significant predictors of survival time (P less than 0.03). In the 17 evaluable patients, the response rate was 47%. PAC is an active regimen in the treatment of endometrial cancer. Larger prospective studies are needed to evaluate whether tumor cytoreduction is important in the treatment of this disease.
 ...
PMID:Treatment of advanced and recurrent endometrial cancer with cisplatin, doxorubicin, and cyclophosphamide. 205 Mar 2

Between October 1985 and January 1989, 33 patients with stage I (31) or clinically occult stage II (2) endometrial cancer at a high risk for recurrence were entered in a prospective study evaluating adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy. Eligibility criteria included grade 2 tumors with middle- or outer-third myometrial invasion (16), grade 3 tumors with any degree of myometrial invasion (17), presence of extrauterine disease with no gross residual (17), or a high-risk histologic subtype including papillary serous (4), adenosquamous (5), or clear cell (1) tumors. Patients received PAC (50/50/500 mg/m2) at 4-week intervals for six cycles. Thirty patients (90%) completed therapy. Toxicity included severe neutropenia in 14 patients, neutropenic sepsis in 2 patients, and doxorubicin-related cardiomyopathy in 1 patient. There were no treatment deaths. Current median follow-up is 25 months. Nine patients (27%) have developed a recurrence, 7 of whom died, after a median interval of 14 months. Eight of the 9 with recurrence initially had extrauterine disease (P = 0.02). The resulting 2-year actuarial progression-free and overall survival rates were 79 and 83%, respectively. The median progression-free interval was 29 months for patients with extrauterine disease and 45+ months for those with no extrauterine disease (P = 0.02). These results suggest that a phase 3 randomized trial comparing adjuvant PAC with radiation therapy is warranted.
 ...
PMID:Adjuvant chemotherapy with cisplatin, doxorubicin, and cyclophosphamide (PAC) for early-stage high-risk endometrial cancer: a preliminary analysis. 222 40

A phase II combination chemotherapy protocol combining methotrexate, vinblastine, doxorubicin, and cisplatin was designed to evaluate tumor response and survival in patients with advanced/recurrent endometrial carcinoma. Thirty patients with advanced/recurrent endometrial carcinoma were assigned to chemotherapy treatment at 4-week intervals with methotrexate 30 mg/m2 i.v. Days 1, 15, and 22; vinblastine 3 mg/m2 i.v. Days 2, 15, and 22; doxorubicin 30 mg/m2 i.v. Day 2; and cisplatin 70 mg/m2 i.v. Day 2. After a median of four cycles (maximum number two cycles beyond complete regression; minimum six cycles for stable partial regression), we observed objective regression in 20 patients (67%) (95% CI, 50, 84) with complete regression in 8 patients (27%) and partial regression in 12 patients (40%). Median overall survival was 9.9 months (range, 0.3-34.2), and median survival of responders was 11.0 months (range, 2.6-34.2) from initial date of response. Toxicity was substantial with two treatment-related deaths and consisted predominantly of neutropenia (grade 3 or greater in 93% of the patients), alopecia, nausea, emesis, stomatitis, and azotemia. In conclusion, MVAC is a highly active outpatient chemotherapy regimen in patients with advanced/recurrent endometrial carcinoma, achieving a high complete and partial response rate. Toxicity is substantial in this elderly patient population.
 ...
PMID:Phase II trial of methotrexate, vinblastine, doxorubicin, and cisplatin in advanced/recurrent endometrial carcinoma. 762 11

Because extrapelvic failure is common in women with high-risk endometrial carcinoma, the curative impact of adjuvant irradiation is limited. To address the issue of systemic failure, we prospectively treated 62 at-risk patients with postoperative chemotherapy between October 1985 and April 1992. Patients were considered eligible if they had grade 2 disease with mid- or outer one-third myometrial invasion, grade 3 tumor with any myometrial invasion, completely resected extrauterine disease, or variant histology (clear cell, papillary serous). Adjuvant therapy consisted of intravenous cisplatin (50 mg/m2), doxorubicin (50 mg/m2), and cyclophosphamide (500 mg/m2) given every 4 weeks for six courses. Toxicity was moderate: 31 patients (50%) had grade 3/4 neutropenia; dose reductions were mandated in 39 cases. However, there were only four hospital admissions for toxicity during 366 treatment cycles. All but three patients completed planned treatment. Recurrences have been noted in 14 of 29 patients with extrauterine disease and in 8 of 33 without. Eighteen of the 22 recurrences (82%) were outside the pelvis. At this writing, 17 patients with recurrence were dead, and 4 are alive with disease. Median time to recurrence was 13 months. Observed progression-free intervals for those with and without extrauterine disease are 26 and 36+ months, respectively, over a median follow-up period of 37 months. Actuarial 3-year survivals for those with and without extrauterine spread were 46 and 82%, respectively. Although adjuvant PAC did not prevent distant failure in women with extrauterine disease, the survival rate was greater than that anticipated for patients with disease confined to the uterus. A randomized trial comparing adjuvant irradiation to PAC is warranted in this subset.
 ...
PMID:Postoperative adjuvant cisplatin, doxorubicin, and cyclophosphamide (PAC) chemotherapy in women with high-risk endometrial carcinoma. 795 65

Cisplatin and the combination of cisplatin, doxorubicin, and cyclophosphamide have documented activity in women with advanced or recurrent endometrial adenocarcinoma. However, response duration has been short and toxicity is substantial. To determine if similar activity could be obtained with less morbidity, we prospectively treated 33 patients with 360 mg/m2 carboplatin given intravenously every 28 days. Mean patient age was 69 years (range 40-86); all had a Zubrod functional status of 2 or less. Seventeen patients had advanced primary tumors, and 16 had recurrent disease. Prior treatment included surgical resection in 29 cases, hormonal agents in 7, and radiotherapy in 22. No patient had received prior chemotherapy. Mean treatment was 5.7 cycles. Nine of 27 patients (33%) with measurable disease had objective responses, including three complete and six partial responses. Nonresponders included 10 patients with stable disease and 8 whose disease progressed while on treatment. Median time to response was 3 months. Median progression-free survival for responders and nonresponders was 5 and 4 months, respectively. At analysis, 20 patients had died of disease, 7 were alive with disease, and 6 were clinically free of disease. Disease-free patients include 1 with a complete response and 5 who began treatment without measurable disease. Median follow-up for surviving patients was 18 months (range 4-32). Treatment toxic effects were minimal and largely limited to myelosuppression; 3 patients had grade 3 thrombocytopenia, 1 had grade 3 neutropenia, and 5 had grade 3 anemia. Carboplatin has define activity in endometrial carcinoma and offers a well-tolerated palliative therapeutic alternative.
 ...
PMID:Treatment of advanced or recurrent endometrial carcinoma with single-agent carboplatin. 811 51

It has been reported that the antitumor effect of CPT-11 is manifested through the inhibition of topoisomerase I by SN-38 which is an active metabolite of CPT-11 produced by intracellular carboxylesterase, and that CPT-11 is effective against recurrent ovarian carcinoma. We investigated the antitumor effect and adverse reactions in the combined therapy with CPT-11 and CDDP in patients with prior chemotherapy for recurrent carcinoma, and in 7 patients without prior chemotherapy, consisting of 4 patients with postoperative adjuvant chemotherapy for clear cell carcinoma and 3 patients with metastatic ovarian carcinoma. CDDP was administered on day 1 and CPT-11 was administered three times on days 1, 8 and 15. The dose of both CDDP and CPT-11 was 50 mg/m2 or 60 mg/m2. Adverse reactions were investigated in all patients and the antitumor effect was assessed in 12 patients with recurrent carcinoma who had measurable lesions. (1) The DLF was neutropenia. The neutrophil count nadiar occurred on day 18 or 19. Grade 3 or 4 adverse reactions were observed in 60% or more of the patients, but they disappeared following short term administration of G-CSF. In patients with recurrent carcinoma given CDDP and CPT-11 at 60 mg/m2, the incidence of grade 3 or 4 adverse reactions and number of occasions on which CPT-11 administration had to be postponed were higher than those in patients given 50 mg/m2. (2) Mild platelet reduction was observed. (3) Grade 3 or 4 diarrhea was observed in 3.2% of patients with recurrent carcinoma and in 7.7% of patients with metastatic ovarian carcinoma. (4) The antitumor effect was evaluated in 12 patients with recurrent carcinoma: CR in 2 patients. PR in 3, NC in 6, and PD in one. The response rate was 41.7%. (5) An antitumor effect was observed in 2 patients with serous carcinoma and in one patient each with mucous carcinoma, clear cell carcinoma and endometrial carcinoma. In conclusion, adverse reactions caused by the combination therapy with CPT-11 and CDDP (CPT-11: 50-60 mg/m2 on days 1, 8 and 15, CDDP: 50-60 mg/m2 on day 1) can be relieved by short term administration of G-CSF and it is suggested that the combination therapy may be effective in treating ovarian carcinoma.
 ...
PMID:[Combination of irinotecan hydrochloride (CPT-11) and cisplatin as a new regimen for patients with advanced ovarian cancer]. 884 Oct 50

Oral etoposide has activity in a wide variety of tumors and is well tolerated. Therefore, the efficacy of oral etoposide was assessed as a treatment of metastatic endometrial cancer. To be eligible for this group-wide Southwest Oncology Group trial, patients had to have histologically proven metastatic or recurrent endometrial carcinoma; no previous cytotoxic therapy; and adequate renal, hepatic, and hematologic function, and they had to have given informed consent. Therapy consisted of oral etoposide, 50 mg daily on days 1-21 on a 28-day schedule. Therapy was continued in the absence of toxicity or disease progression. Forty-four eligible women, with a median age of 68 years (range 38-84 years) were treated. Radiotherapy had been delivered to 33 and hormomal therapy to 21. The median duration of therapy was 69 days (range 7-510 days). The treatment was well tolerated. Only one patient had grade 4 neutropenia, and a second had grade 4 anemia. Three patients had grade 3 nausea. One complete and five partial responses (14%) were observed. An additional four patients had unconfirmed responses. Tumor regressions were noted in nodes, bone, and visceral organs. While oral etoposide has only a modest level of activity when used in chemonaive patients, the minimal toxicity of this drug makes it a candidate for use in combination chemotherapy.
 ...
PMID:Phase II trial of oral etoposide in recurrent or refractory endometrial adenocarcinoma: a southwest oncology group study. 1047 5

The purpose of this study was to evaluate the combination of paclitaxel and carboplatin in patients with endometrial cancer who have high-risk histopathologic criteria with vessel permeation and low grade, advanced or recurrent disease. The combination of paclitaxel (180 mg/m2 over 3 hours) and carboplatin (dosed at an area under the curve of 5-6) was given intravenously every 3 weeks. Response and toxicity were evaluated according to the Japan Society of Clinical Oncology's response and adverse effect criteria. Eighteen patients were entered in this study and a total of 94 courses were administered. Eleven patients had evaluable lesions. Complete and partial responses were achieved in 5 (45.5%) and 3 (27.3%) patients, respectively. Grade 3 or 4 leukopenia and neutropenia occurred in 49.2% and 90.5% of the patients. G-CSF support was needed in 52.4% of the patients. Only one patient received a platelet transfusion. As a high response rate was obtained, this regimen is considered to be promising treatment for endometrial carcinoma. Prospective comparative study between this combination therapy and the conventional therapy for endometrial carcinoma is warranted.
 ...
PMID:[Evaluation of paclitaxel and carboplatin in patients with endometrial cancer]. 1070 Aug 97

We evaluated the effects of a combined chemotherapy regimen on endometrial carcinoma in 14 patients with lymph node metastasis. After surgery, the patients were treated with 3 cycles of chemotherapy (PVP regimen) every 4 weeks. The PVP regimen consisted of 75 mg/m2 cisplatin on day 1, 40 mg/m2 pirarubicin (P) on day 1, and 75 mg/m2 etoposide (VP-16: V) on days 2, 3 and 4. The effect of adjuvant chemotherapy was evaluated based on progression-free survival (PFS), overall survival (OS), and adverse effects. The 5-year PFS rate was 52% [95% confidence interval (CI), 10-94%], and the 5-year OS rate was 50% (95% CI, 16-84%). The major toxicity was myelosuppression. One hundred percent of patients had neutropenia above grade 3, but all recovered from myelosuppression. PVP therapy may be an effective adjuvant therapy for endometrial carcinoma patients with lymph node metastasis used as an alternative to radiation therapy.
 ...
PMID:Postoperative adjuvant chemotherapy with cisplatin, etoposide, and pirarubicin for endometrial carcinoma patients with lymph node metastasis: A pilot study. 1094 43


1 2 Next >>