HER-2/neu oncogene amplification and expression in breast and ovarian cancers.
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Breast Neoplasms↗
Biomedical subjects
C L Edwards
Publications and source records attributed to C L Edwards.
Effect of virus-modified tumor cell extracts, autologous mononuclear cell infusions and interleukin-2 on oncolytic activity of effector cells of patients with advanced ovarian cancer.
We studied the biological responses of six ovarian cancer patients after intraperitoneal (i.p.) injections of virus-modified tumor cell extracts (VMTE) and autologous peripheral blood mononuclear cells, collected by leukapheresis after two injections of VMTE. VMTE was prepared from allogeneic ovarian cell lines, OV2774 and CaOV3, modified by influenza virus, A/PR8/34. A dose of 9 mg VMTE was given i.p. in total of 2-4 injections, and (1-9) x 10(8) autologous mononuclear cells were infused i.p., 24 h after the second VMTE injection, and 24 h and 72 h after the third VMTE injection. Both peripheral blood (PB) and peritoneal cavity (PC) effector cell cytotoxicity was significantly enhanced against the K562 cell line in the majority of patients, 24-48 h after the second and third VMTE injections. This was accompanied by a dramatic influx of neutrophils into PC (57-550-fold), increase in absolute numbers of lymphocytes, (including large granular lymphocytes) and monocytes, and resulted also in a significant decrease in the number of ascitic tumor cells (98% reduction). The infusion of autologous mononuclear cells did not appear to influence either cytotoxicity or cell infiltration of the peritoneal cavity. We also investigated the in vitro effect of recombinant interleukin-2 (IL-2) on effector cells from PB and PC from patients before and after VMTE treatment. Cytotoxicity of both of these compartments was significantly potentiated after culture with IL-2. In three out of five VMTE-treated patients, PC cytotoxicity was significantly higher after activation with IL-2 than that of patients before VMTE treatment. These data suggest that VMTE induces regional cellular immunity, which could be further potentiated by culture of PC effector cells with IL-2. Thus, combination of VMTE and IL-2 after regional administration could represent the effective therapy for patients with advanced ovarian cancer.
Adjuvants, Immunologic↗
Gracilis myocutaneous vaginal reconstruction concurrent with total pelvic exenteration.
The gracilis myocutaneous vaginal reconstruction is commonly performed in patients undergoing a total pelvic exenteration. This retrospective review compares the operative and perioperative morbidity in 107 patients who underwent reconstruction with that in 44 patients who did not have reconstruction. With incorporation of the reconstructive procedure, there were no increases in operating time, blood loss, or length of hospitalization. Before 1980, 65% of patients experienced prolapse of the neovagina; in 25% it was severe. The frequency of prolapse has since been decreased to 16% (6% severe) because of several modifications to the initial technique. Modifications have included using smaller flaps, anchoring the neovagina to the levator and retropubic fascia, and, when necessary for mobilization, ligating the neurovascular pedicle. With these modifications, 66% of patients also remained free of wound breakdown or necrosis. The frequency of severe necrosis has decreased from 24% to 13%. The anatomic result of the vaginal reconstructions appears to have been enhanced by these changes in technique.
Female↗
Secondary cytoreductive surgery for recurrent epithelial ovarian cancer.
Thirty patients with recurrent epithelial ovarian carcinoma who underwent secondary tumor-reductive surgery at M. D. Anderson Cancer Center were studied retrospectively. All had been initially treated by primary reductive surgery and postoperative chemotherapy and had a period of clinical remission of at least 6 months thereafter. Ninety percent of patients had grade 2 or 3 tumors. In 17 (57%), residual tumor volume was reduced to less than 2 cm. There were no postoperative deaths, but 40% of patients suffered postoperative morbidity, mostly prolonged ileus. Median survival after second surgery was 16.3-18 months for patients with residual tumor volume less than 2 cm and 13.3 months for those with residual volume greater than 2 cm (nonsignificant). When the second surgery followed the first by less than 18 months, survival was a median of 13.5 months after the second operation as compared with 19 months when the interval was 18 months or longer (nonsignificant). Twenty-two patients received postsurgical chemotherapy; only 11% of those who were evaluable responded. Although secondary tumor-reductive surgery for recurrent ovarian cancer is technically feasible, in the absence of an efficacious second-line medical therapy, its value is limited.
Adult↗
Treatment of advanced epithelial ovarian cancer with cisplatin and cyclophosphamide.
Between June 1981 and June 1984, 50 patients with stage III or IV epithelial ovarian cancer underwent initial surgery followed by combination chemotherapy with cisplatin 50 mg/m2 iv and cyclophosphamide 500-1000 mg/m2 iv at 28-day intervals. No patients with borderline or well-differentiated tumors were included. If patients were clinically disease-free after 12 cycles of therapy, a second-look laparotomy was performed. A complete response was noted in 12 patients (24%), 11 of whom were surgically evaluated. A partial response was noted in 4 patients (8%), 3 of whom were surgically evaluated. Thirty-four patients (68%) had no response to therapy. The median progression-free survival (PFS) for the entire group was 19.8 months, with a median survival of 27 months. Patients with less than or equal to 2 cm residual disease had a superior median PFS (25.4 months vs 18 months) and median survival (29.4 months vs 19.5 months) to those patients with greater than 2 cm residual disease. Patients who underwent primary debulking had a longer median survival than patients who underwent "interval" debulking after two to four cycles of chemotherapy (29.2 months vs 17.3 months). Thirteen patients (26%) are alive without evidence of disease, 4 patients are alive with disease, and 33 patients are dead of disease. Toxicity was very moderate. In summary, the activity and toxicity of the combination of cisplatin and cyclophosphamide compare favorably to other cisplatin combination regimens.
Adult↗
Sleep-disordered breathing in healthy aged persons: one-year follow-up of daytime sequelae.
We studied the waking medical, sleep, and psychological status of 28 healthy older persons who had undergone nocturnal polysomnography and daytime assessment approximately 1-year earlier. In a previous report based on this sample, we found that sleep-disordered breathing (SDB) indices were not related to concurrent measurements of daytime functioning. However, in the present study, we observed relationships between the original SDB indices and several measures of cardiopulmonary functioning obtained 1 year later. At follow-up, subjects with originally high levels of SDB had significantly higher systolic blood pressure and poorer pulmonary function test results, were more likely to report irregular heartbeats in the previous year, and had experienced more disruptive snoring than the remaining subjects. When combined with other recent data, these results raise the possibility that SDB exerts an insidious pathological influence on the health and daytime functioning of otherwise healthy older persons.
Aged↗
Randomized comparison of viral oncolysate plus radiation and radiation alone in uterine cervix carcinoma.
A randomized, controlled study was performed in patients with high-risk, untreated squamous cell carcinoma of the uterine cervix to evaluate the adjunctive use of viral oncolysate (VO) prepared from the SW756 cell line. Seventy-five patients were stratified by tumor volume and randomized to receive radiation therapy (RT) alone or RT plus intradermal immunization with VO. Fifty-one (68%) patients relapsed with a median survival (MS) of 29.1 months and a median progression-free interval (MPFI) of 18.0 months. No differences in MS or median PFI were observed by treatment arm or site of relapse, although a trend toward improved MS and median PFI in patients with small-volume primary lesions was suggested. Serum surface-binding antibody activity (greater than or equal to 1:8) to the SW756 cell line was detected in 14 of 41 unselected patients prior to therapy. Virus hemagglutination inhibitory activity (greater than or equal to 1:8) was detected in 37 of 41 patients before treatment. four-fold increases in titer were observed to the SW756 cell line in 83% and to influenza in 74% of patients tested after immunization. Preirradiation measurements of phytohemagglutinin-induced blastogenesis by the relative proliferation index (RPI) method in 39 patients revealed RPI values less than 0.58 in nine patients, eight of whom relapsed. At 3-6 months after the initiation of irradiation, 32 of 39 patients had values less than 0.58. Patients in the RT group with values less than 0.58 had significantly more relapses than those who received RT plus VO.
Adult↗
Lymphokine activity in malignant effusions after intracavitary viral oncolysate.
Six patient with malignant effusions (five with ascites and one with malignant pleural effusion) due to refractory ovarian carcinomatosis, received intracavitary injections of ovarian viral oncolysate (VO). Measurements were made of the intracavitary activities of T cell growth factor (TCGF-IL-2) and B cell growth factor 12-kD (BCGF) and these were correlated with the clinical activity and cytologic changes in the malignant effusions. Both BCGF and IL-2 activities were demonstrated in malignant effusions prior to therapy although these were relatively higher for BCGF. Increases in the activities of both lymphokines were observed in the post VO treatment samples ranging from 4.1% to 45.0% for BCGF and 4.8% - 33.9% for IL-2. One patient who exhibited marked clinical improvement accompanied by mononuclear cell infiltrates and diminution of ascitic fluid malignant cells, also had elevation of lymphokine activities after repeated VO injections. These data provide further support for the role of VO as inducers of regional immunity.
Ascitic Fluid↗
Recombinant IL-2-activated NK cells mediate LAK activity against ovarian cancer.
We investigated the ability of endogenous and recombinant interleukin-2 (IL-2)-stimulated NK cells from normal donors and ovarian cancer patients to mediate lysis of ovarian tumors, and found that peripheral blood (PB) mononuclear cells of normal donors or cancer patients did not display tumoricidal activity against ovarian cell line or fresh ovarian tumors. In addition, ovarian cancer patients displayed a defect in NK-cell activity against the highly NK-sensitive target, K-562. However, lytic activity against ovarian tumors (including cultured and primary tumors) was induced and that against K-562 was potentiated in PB of normal donors and PB and peritoneal cavity of ovarian cancer patients after enrichment of LGL on Percoll density gradient or after stimulation of effector cells with recombinant IL-2 in vitro. The IL-2-generated cytotoxic cells in PB were characterized as NK cells displaying CD16+, NKH1 (Leu-19)+, CD3- and CD5- phenotype, while those in the peritoneal cavity were predominantly CD16-, NKH1+, CD3- and CD5-. Studies on the mechanism of IL-2-dependent generation of cytotoxicity showed that such an effect was mediated via recruitment of tumor-binding cells as well as by an increase in the frequency of cytotoxic cells.
Cytotoxicity, Immunologic↗
Viral oncolysates in patients with advanced ovarian cancer.
Viral oncolysates (VO) derived from two cultured ovarian carcinoma cell lines infected with influenza A/PR8/34 were administered intraperitoneally (IP) to 40 patients with advanced ovarian carcinoma, including 31 with late-onset ascites and 5 with pleural effusions. PR8 virus-specific antigens and ovarian tumor-associated antigens have been demonstrated on two oncolysates designated OVO1 and OVO2. Thirty-five patients received 9 mg of a 1:1 mixture of OVO1 and OVO2, 5 patients received one or the other. During the first month three IP schedules were evaluated, i.e., single, biweekly, and weekly, which were followed by monthly injections. Intrapleural (IP1) injections of a 3.0-mg 1:1 mixture of OV1 and OV2 were administered to 3 patients concurrently with initial IP injections and to 2 patients following later development of pleural effusions. In 7 patients ascites disappeared; in 5 of these the number of cytologically detected malignant cells was markedly reduced, in 1 pleural effusion disappeared, and in 3 tumor masses were reduced. Tumor masses shrank also in 2 patients without ascites. Tumor reduction conformed to standard response criteria in 2 of the 5 patients. Response duration in the 9 responding patients lasted from 3 to 19 months and survival durations 4 to 42 months. Disease symptoms in 7 patients improved noticeably. Two of the 9 responders later developed unilateral pleural effusions that responded for 7 and 15+ months to a single IP1 injection. Seventeen patients experienced one or more treatment side effects including fever, nausea or anorexia, malaise, abdominal pain, and arthralgia, but in only 2 patients, both on the weekly schedule, was toxicity severe enough to require treatment withdrawal. Humoral responses to viral and tumor cell-surface antigens were frequently observed in patients demonstrating clinical activity.
Adult↗
Recurrent cervical carcinoma after radical hysterectomy.
The characteristics of recurrent carcinoma following radical hysterectomy and pelvic lymphadenectomy for cervical carcinoma are not well known. Disease recurrence was noted in 27 of 249 patients (11%) with stage IB cervical carcinoma who were treated with a primary surgical approach between January 1962 and December 1984. Fourteen recurrences (52%) occurred within 1 year of surgery, and 24 (89%) within 2 years. Patients with pelvic node metastases or adenocarcinoma had a significantly higher recurrence rate than did patients with negative nodes (33% vs 8%) or with squamous carcinoma (22% vs 8%). Seventeen patients (63%) had disease recurrence in the pelvis or vulva and 12 of these patients had recurrences within 1 year. Eight patients developed asymptomatic pelvic or vulvar recurrences, and all were diagnosed within 1 year. Ten patients (37%) developed recurrences outside the pelvis and 8 of these experienced recurrence after 1 year. Successful treatment after recurrence was independent of clinical or histopathologic parameters except site of recurrence. Eight of 15 patients (53%) who were treated with irradiation for a recurrence in the pelvis or vulva are free of disease 10 to 126 months (median, 48 months) after recurrence. Since irradiation can aid in salvaging patients with recurrent cervical carcinoma confined to the pelvis following radical surgery, clinical vigilance for this site of recurrence is emphasized.
Adenocarcinoma↗
Hyperfractionated split-course whole abdominal radiotherapy for ovarian carcinoma: tolerance and toxicity.
Whole abdominal irradiation after chemotherapy and second look laparotomy for advanced ovarian carcinoma is poorly tolerated because of hematologic toxicity that frequently necessitates interruption or abandonment of treatment. A new treatment strategy using a hyperfractionated split course schedule to deliver a total of 30 Gy in 30 fractions over 6 weeks was designed in an attempt to overcome this problem, while not compromising the tolerance of late reacting normal tissues. Of 23 patients treated between August 1984 and June 1986, only one failed to complete therapy as scheduled. Six patients with gross residual disease also received a limited field boost of 15 Gy in 15 fractions after completion of treatment to the whole abdomen. None of these six patients achieved disease control, and five required surgery for intestinal obstruction with pathologic evidence of radiation bowel injury. Of the 17 patients who received no boost, five developed gut obstructions associated with tumor recurrence and not attributable to irradiation. We conclude that whole abdominal irradiation using the hyperfractionated split course schedule without a boost is safe and feasible but its therapeutic efficacy appears confined to subsets of patients with no visible residual disease at the time of second look laparotomy, or in whom all visible residual tumor can be resected.
Adult↗
Diagnosis of recurrent cervical carcinoma after radical hysterectomy.
A standard surveillance program for cervical carcinoma patients treated with radical hysterectomy is reviewed. Between 1962-1984, 249 patients with stage IB cervical carcinoma treated with radical hysterectomy and pelvic lymphadenectomy were entered in the surveillance program. Of the 27 patients (11%) diagnosed with recurrent carcinoma, 17 (63%) were identified by clinical history, 22 (81%) by physical examination, five (18%) by vaginal cytology, six (22%) by chest radiography, and eight (30%) by renal contrast imaging. Combined clinical history and physical examination identified 24 patients (89%) with recurrent carcinoma. Disease recurrence was detected by vaginal cytology in one asymptomatic patient with a normal examination. The recommended surveillance procedures for patients with cervical carcinoma after radical hysterectomy include clinical history, physical examination, and vaginal cytology. Chest radiography and renal contrast imaging should be reserved for symptomatic patients.
Cytodiagnosis↗
Prognostic factors in stage II endometrial carcinoma.
The rarity of Stage II endometrial carcinoma and variable treatment modalities have made the evaluation of prognostic factors difficult. Clinical, surgical, and pathologic characteristics were evaluated in 64 patients treated with whole pelvic irradiation and intracavitary radium followed by hysterectomy at The University of Texas M.D. Anderson Hospital and Tumor Institute from January 1965 to December 1983. Comparison of 5-year actuarial survival rates revealed the following statistically significant categories: age, grade, depth of myometrial invasion, disease extent at surgery including lymph node metastases, and pelvic cytology. Race, weight, and cell type were not significant prognostic factors. Evaluation of prognostic factors at surgery includes pelvic and para-aortic lymph node biopsies, omental biopsy, pelvic cytologic washings, and biopsy of any suspicious tissues. Patients with adverse prognostic factors are candidates for trials with adjuvant therapy.
Actuarial Analysis↗
Intrahepatic infusional therapy for metastatic ovarian carcinoma.
Twenty-four women with ovarian carcinoma that had metastasized to the liver were treated with intrahepatic infusional therapy. No consistent drug regimen was used. There were no complete responders; however, 33% had a partial response. All responses were noticed after the first course of therapy. The median length of response was 6.3 months. The median survival from the time of the first hepatic infusion was 7.5 months for all patients. In this series, there were two treatment-related deaths, one secondary to the chemotherapy, the other to improper catheter placement. Because of the multiplicity of chemotherapy regimens employed, no definite conclusions can be made concerning the efficacy of intrahepatic infusional therapy for metastatic ovarian carcinoma. It is suggested that its future use be restricted to patients with disease limited to the liver and who are being treated according to a study protocol.
Adolescent↗
High-dose doxorubicin infusion therapy for disseminated mixed mesodermal sarcoma of the uterus.
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.
Adult↗
Cisplatin therapy for disseminated mixed mesodermal sarcoma of the uterus.
Eighteen patients with metastatic mixed mesodermal sarcoma of the uterus received cisplatin therapy at the University of Texas (UT) M.D. Anderson Hospital and Tumor Institute at Houston. The dose of cisplatin varied from 75 mg/m2 to 100 mg/m2. Previous therapy included surgery in 11 patients, radiotherapy in two patients, and surgery plus radiotherapy in four patients. One patient had no prior therapy. Seven patients had also received prior chemotherapy with doxorubicin. Of 12 patients with measurable disease, one (8%) had a complete response and four (33%) had a partial response for an overall response rate of 42%. The median progression-free survival of patients treated with cisplatin as first- and second-line therapy was 4.5 and 5.5 months, respectively. Cisplatin demonstrated moderate activity with mild toxicity in this group of patients with metastatic mixed mesodermal uterine sarcomas. Further studies including cisplatin-containing combination regimens seem to be warranted.
Aged↗
Treatment of malignant nondysgerminomatous germ cell tumors of the ovary with vinblastine, bleomycin, and cisplatin.
Fifteen patients with malignant nondysgerminomatous germ cell tumors of the ovary seen at The University of Texas M. D. Anderson Hospital and Tumor Institute at Houston, were treated with a combination of vinblastine, bleomycin, and cisplatin (VBP). All patients underwent initial surgery: biopsy alone in one patient, unilateral salpingo-oophorectomy in ten patients, and bilateral salpingo-oophorectomy with or without hysterectomy in four patients. Seven patients received VBP as primary postoperative therapy. One patient died of progressive disease at 15 months following diagnosis. The other six patients are alive without evidence of disease 9 to 47 months from the time of diagnosis. Eight patients received VBP as second-line treatment; three patients had a complete response to therapy and are surviving disease-free 41 to 71 months from the time of diagnosis. Four patients treated secondarily had a partial response; three of these patients subsequently developed progressive disease and died, while one patient survived after undergoing salvage therapy with an etoposide-containing regimen. One patient had no discernible response to VBP therapy and died. The VBP regimen represents an aggressive, moderately toxic, short-term combination regimen that has promising activity against malignant germ cell tumors of the ovary.
Adolescent↗