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Biomedical subjects

A F Fuller

Publications and source records attributed to A F Fuller.

At least 19 recordsLinked to original sources
PubMed2006

Phase I/II dose finding study of combination cisplatin and gemcitabine in patients with recurrent cervix cancer.

OBJECTIVES: To evaluate the toxicity and efficacy of cisplatin and gemcitabine in women with recurrent cervical cancer. METHODS: A multi-institutional phase I/II dose finding study of cisplatin and gemcitabine delivered to women with recurrent previously radiated cervical carcinoma. RESULTS: Twenty eight patients were enrolled. The mean and median age of patients was 51 years (age range 35 to 70 years). Chemotherapy was given on a 28-day cycle; cisplatin was administered at a fixed dose of 50 mg/m(2), day 1 and gemcitabine, days 1, 8, and 15. Gemcitabine doses started at 600 mg/m(2) (dose level 1) and were escalated by 100 mg/m(2)/dose level until 1000 mg/m(2) (dose level 5). Twenty seven patients were evaluable for toxicity and disease response, and 75 cycles of chemotherapy were administered. Toxicities were predominantly hematological; 18% of patients experienced grade 3 anemia, 37% grade 3 and 11% grade 4 leukopenia, 41% grade 3 neutropenia, and 26% grade 3 thrombocytopenia. The maximally tolerated dose (MTD) was not reached. One patient experienced a dose-limiting toxicity on dose level 2 (febrile neutropenia). One patient had a CR and 3 patients had a PR to therapy (15% response rate), 41% of patients had SD, and 44% had progression of cancer. Median survival was 11.9 months. CONCLUSION: Although this 28-day gemcitabine and cisplatin regimen in recurrent cervix cancer has tolerable toxicity, 21-day regimens are recommended because of improved practicality, higher dose intensity, and higher response rates.

Adult↗
PubMed2005

A phase I clinical trial of continual alternating etoposide and topotecan in refractory solid tumours.

The goal of this phase I study was to develop a novel schedule using oral etoposide and infusional topotecan as a continually alternating schedule with potentially optimal reciprocal induction of the nontarget topoisomerase. The initial etoposide dose was 15 mg m(-2) b.i.d. days (D)1-5 weeks 1,3,5,7,9 and 11, escalated 5 mg per dose per dose level (DL). Topotecan in weeks 2,4,6,8,10 and 12 was administered by 96 h infusion at an initial dose of 0.2 mg m(-2) day(-1) with a dose escalation of 0.1, then at 0.05 mg m(-2) day(-1). Eligibility criteria required no organ dysfunction. Two dose reductions or delays were allowed. A total of 36 patients with a median age of 57 (22-78) years, received a median 8 (2-19) weeks of chemotherapy. At DL 6, dose-limiting toxicities consisted of grade 3 nausea, vomiting and intolerable fatigue. Three patients developed a line-related thrombosis or infection and one subsequently developed AML. There was no febrile neutropenia. There were six radiologically confirmed responses (18%) and 56% of patients demonstrated a response or stable disease, typically with only modest toxicity. Oral etoposide 35 mg m(-2) b.i.d. D1-5 and 1.8 mg m(-2) 96 h (total dose) infusional topotecan D8-11 can be administered on an alternating continual weekly schedule for at least 12 weeks, with promising clinical activity.

Adult↗
PubMed2001

A Phase I-II study of 96-hour infusional topotecan and paclitaxel for patients with recurrent Müllerian tumors.

BACKGROUND: Topotecan and paclitaxel are schedule dependent chemotherapeutic agents with activity against ovarian carcinoma. A Phase I-II study in which both drugs were administered concurrently by 96-hour, continuous, intravenous infusion was performed to determine the maximum tolerated dose (MTD), toxicities, pharmacokinetics, and efficacy of the combination. METHODS: Women with ovarian or primary peritoneal carcinoma and documented recurrent disease were eligible for the study. The dose of topotecan was escalated from 1.6 mg/m(2) while maintaining the paclitaxel dose constant at 100 mg/m(2). Plasma concentrations of both drugs were monitored daily during the first cycle of therapy. RESULTS: Forty-five patients with a median age of 54 years (range, 42-70 years) received 181 cycles of therapy. Five patients were recruited to each of four dose levels (topotecan 1.6 mg/m(2), 2.0 mg/m(2), 2.8 mg/m(2), and 3.6 mg/m(2)), and an additional 25 patients were treated at the MTD (Phase II). Neutropenia and thrombocytopenia became dose limiting toxicities (DLT) at the fourth dose level. Emesis, mucositis, peripheral neuropathy, diarrhea, and alopecia were mild. Twenty patients (44%) had line-related occlusion, thrombosis, or infection. The mean values (+/- standard deviation) of the apparent steady-state plasma concentrations at the Phase II doses were 2.3 nM +/- 0.5 nM for topotecan lactone, 5.6 nM +/- 2.1 nM for total topotecan, and 40.1 nM +/- 16.8 nM for paclitaxel. There were seven partial responses (Phase II) contributing to an objective response rate of 28% and a median survival time of 11.7 months (range, 0.6-20.1 months). CONCLUSIONS: Topotecan at a dose of 2.8 mg/m(2) and paclitaxel at a dose of 100 mg/m(2) administered by concurrent, 96-hour, continuous intravenous infusions shows activity against tumors of Müllerian origin.

Adult↗
PubMed2001

The clinical utility of liposomal doxorubicin in recurrent ovarian cancer.

OBJECTIVES: The aim of this study was to determine the efficacy and toxicity of single agent off-protocol, liposomal doxorubicin (Doxil Alza), in consecutive patients with recurrent ovarian cancer and to investigate the influence of HER-2/neu expression on response to liposomal doxorubicin. PATIENTS AND METHODS: Retrospective analysis of 72 consecutive patients treated, typically with liposomal doxorubicin 40 mg/m(2) q28 days between January 1997 and December 1998. Results. Twenty-nine patients (40%) had platinum- and taxane-resistant tumors. Nineteen patients (27%) responded with clinical or radiological evidence of response with reduction in CA-125 of >50%. One complete response (CR) and 7 partial responses (PRs) occurred in platinum- and taxane-resistant patients (radiological response (RR) 29%) and 8 PRs occurred in patients with visceral metastases (RR 28%). Time to progression was 5.3 (2.1-12.1) months. Only 7 dose delays (3%) and 20 dose reductions (8%) were necessary in 265 cycles of treatment. Hematological toxicity was generally mild with grade (Gr) > or =III neutropenia in 1 (2%), Gr > or =III thrombocytopenia in 1 (1%), and Gr > or =III anemia in 8 patients (11%). One patient (1%) was admitted with fever and neutropenia. Other toxicity was minimal with Gr > or =III mucositis occurring in 3 patients (4%). Gr > or =III cutaneous toxicity was seen in 6 patients (8%). Three patients (4%) had a >10% fall in ejection fraction but there was no unequivocal clinical heart failure. CONCLUSIONS: The data suggest that liposomal doxorubicin is an active drug in both taxane- and platinum-sensitive and resistant recurrent ovarian cancer. Liposomal doxorubicin is associated with tolerable toxicity and is particularly well tolerated in patients with multiple prior lines of treatment.

Adult↗
PubMed2001

Successful pregnancy after high-dose cyclophosphamide, carboplatinum, and taxol with peripheral blood stem cell transplant in a young woman with ovarian carcinoma.

BACKGROUND: Both ovarian carcinoma and high-dose chemotherapy tend to preclude future pregnancies. CASE: We report a case of a young woman with borderline ovarian carcinoma and invasive tumor implants who underwent surgical debulking with preservation of future fertility followed by carboplatinum, paclitaxel (Taxol), and subsequent high-dose chemotherapy with subsequent peripheral blood stem cell rescue as part of a phase I clinical trial. After a brief period of amenorrhea, the patient had a successful pregnancy that was complicated by a spontaneous abortion in the first trimester. Several months later she conceived and delivered a healthy baby at term. CONCLUSIONS: To our knowledge this is the first reported case of pregnancy after high-dose chemotherapy with stem cell transplant in a woman with ovarian carcinoma.

Adult↗
PubMed2001

Endometrial cancer in women 40 years old or younger.

OBJECTIVE: The aim of this study was to characterize endometrial cancer in women 40 years of age and younger, with special attention toward body-mass index (BMI). METHODS: A retrospective review of women age 40 and under with endometrial cancer was performed. Patients were identified via tumor registry data as well as a search of pathology department diagnoses over the dates 1980-1998. Data were abstracted regarding tumor grade and histology, stage, treatment, smoking, use of oral contraceptives, BMI, medical and family history, parity, and survival. Data were also collected with regard to uterine conservation and pregnancies following endometrial cancer diagnoses. RESULTS: Ninety-five patients were identified. The age range was 24-40 years (median 37) with BMI ranging from 17.5 to 63.6 (median 28.4). Forty-eight patients (52%) were not obese, with BMI < 30. Seventy-six patients (80%) had stage I disease and 60 patients (63%) had grade 1 disease. All but 4 patients had endometrioid histology. Women with BMI < 25 were more likely to have advanced disease (P = 0.04) and more likely to have high-risk histology (P = 0.02). Of the 4 patients with high-risk histology (clear cell or serous papillary), all had BMI < 25. Twelve patients were treated medically rather than surgically, and 4 patients achieved pregnancy, with 5 live births. CONCLUSION: Women under 40 who are not obese are at higher risk of both advanced disease and high-risk histology. Further study at the molecular and genetic level is ongoing in our laboratory to determine whether the mechanism of disease is different in slender woman.

Adenocarcinoma↗
PubMed2000

Intraoperative radiation therapy in the treatment of pelvic gynecologic malignancies: a review of fifteen cases.

OBJECTIVE: The aim of this study was to review the experience with intraoperative radiation therapy (IORT) in the treatment of gynecologic pelvic malignancies at the Massachusetts General Hospital. METHODS: From July 3, 1996, through July 28, 1999, 15 patients were treated with IORT for gynecologic malignancies in a dedicated IORT operating room suite at the Massachusetts General Hospital. Hospital medical records, radiation oncology records, and office charts were reviewed on all patients treated with IORT. IORT was given in the presence of positive surgical margins and where the doses needed for adjuvant postoperative external beam radiotherapy (EBRT) would exceed those tolerated by normal structures. One patient presented with primary disease and 14 with local or regional recurrence. Follow-up time ranged from 3 to 36 months. RESULTS: Treatment in conjunction with IORT included surgery only (7 patients); preoperative EBRT, preoperative brachytherapy, and surgery (1 patient); preoperative chemotherapy and surgery (2 patients); and surgery and postoperative chemotherapy (5 patients). IORT doses ranged from 10 to 22.5 Gy. At the completion of this review, 4 patients (26.6%) have died, 6 (40%) are alive and free of disease, and 5 (33%) are alive with disease persistence or relapse. Of the 10 patients with gross total resection, 5 are alive and free of disease. Of the 5 women with gross residual disease at the time of IORT, only 1 is alive and free of disease. CONCLUSIONS: The volume of residual disease prior to IORT may be an important prognostic indicator for disease relapse. Both local recurrence and distant metastasis were more common among patients with gross residual disease at the time of IORT. Our institutional experience with IORT further supports the importance of optimal surgical resection.

Adult↗
PubMed2000

Borderline tumors of the ovary: correlation of frozen and permanent histopathologic diagnosis.

OBJECTIVE: To evaluate the correlation between the diagnosis of borderline tumor of the ovary by frozen and permanent pathology. METHODS: All pathology reports with diagnoses of borderline tumor of the ovary between 1980 and 1998 at Massachusetts General Hospital were reviewed. Univariate and multivariable logistic regression models were constructed for patient age, tumor size, histology, presence of bilateral or extraovarian disease, and concurrent diagnosis of endometriosis or endosalpingiosis. RESULTS: We reviewed 140 cases. The average age of patients was 52.3 years. Eighty tumors were serous, 47 mucinous, 11 mixed, and two endometrioid. The mean diameter overall was 13.7 cm (range 1-70 cm), 10.2 cm for serous, and 20.1 cm for mucinous. Diagnoses of borderline tumors by frozen and permanent pathology were consistent in 60% of cases. Frozen section interpreted a benign lesion as malignant (overdiagnosed) in 10.7% of cases, and interpreted a malignant lesion as benign (underdiagnosed) in 29.3%. No variable was a significant predicator of overdiagnosis. In univariate analysis, underdiagnosis was more likely for other types of tumors than serous (P <.001), tumors larger than 20 cm (P =.039), and tumors confined to the ovaries (P =. 009). When all variables were included in a multiple regression model, only histology was a significant predictor of underdiagnosis (P =.039). CONCLUSION: Frozen or permanent pathology reports of diagnoses of borderline tumor were consistent 60% of the time, whereas the positive predictive value of borderline by frozen section was 89.3%. Tumors other than serous are more likely to be misinterpreted.

Adenocarcinoma↗
PubMed1999

Epithelial ovarian carcinoma in the reproductive age group.

BACKGROUND: A retrospective review of women age < or = 40 years with epithelial ovarian carcinoma was undertaken to determine whether patient age and tumor grade are independent prognostic factors for survival, to investigate the survival rate for young women with ovarian carcinoma, and to characterize these young women in terms of reproductive capability. METHODS: The tumor registry of the Massachusetts General Hospital was used to identify cases of ovarian carcinoma diagnosed between January 1980 and July 1996. Patient records and pathology were reviewed. Survival rates were calculated by the Kaplan-Meier method and Cox proportional hazards models were used to determine the independent effect of each variable on survival. RESULTS: Ninety-two tumors epithelial tumors were identified with 46 (50%) classified as borderline. In the univariate analysis, stage (P < 0.001), grade (P < 0.001), residual disease (< or = 2 cm vs. > 2 cm, P < 0.001), and age (< 30 years vs. 31-40 years; P = 0.019) were found to be significant prognostic factors for survival. However, in the multivariate analysis only tumor grade (with borderline tumors assigned a grade of 0) and stage were significant predictors of survival (P < 0.01 for both). The 5-year survival rate for carcinoma patients with advanced disease was 22.9%. Patients with borderline tumors were more likely be diagnosed during an evaluation for infertility and were more likely to have successful live births after carcinoma treatment. CONCLUSIONS: Young women with advanced epithelial carcinoma have a 5-year survival rate similar to that quoted in the literature, despite the use of more aggressive chemotherapeutic regimens. Patients with borderline tumors of any stage have an excellent prognosis for preserving fertility options.

Adult↗
PubMed1999

Diagnostic utility of Müllerian inhibiting substance determination in patients with primary and recurrent granulosa cell tumors.

OBJECTIVES: In this study we evaluated changes in serum Müllerian inhibiting substance (MIS) concentration in a large number of patients with granulosa cell tumors (GCT) to determine whether MIS is elevated at the time of presentation and whether MIS is an index of successful surgical resection and management of recurrences. METHODS: We retrospectively reviewed MIS levels from 17 subjects prior to tumor resection and studied serial MIS samples from 56 subjects following initial tumor resection. Clinical follow-up information was available for 36 of those with postoperative MIS values. Serum MIS was measured by an ELISA. MIS values were compared to a combination of normative values previously established in our laboratory and from more recently obtained samples from older pre- and postmenopausal women, using this assay. RESULTS: Serum MIS was elevated pre-operatively in 6 of 8 (75%) subjects with juvenile GCTs and in 7 of 9 (78%) of those with adult GCTs relative to age-matched controls (76% for both types combined). Post-operative clinical correlation was available for 36 patients. There was no clinical recurrence in 21 subjects with normal or undetectable postoperative values, and incompletely resectable tumor or recurrence was identified in 6 of 15 patients with elevated postoperative values. CONCLUSIONS: The results of this study demonstrate that postoperative serum MIS concentrations may be used to evaluate the completeness of tumor removal following initial surgery and that serial MIS determinations may allow the detection of recurrences.

Adolescent↗
PubMed1999

Predictors of recurrence in surgical stage II endometrial adenocarcinoma.

OBJECTIVE: A retrospective review of surgical stage II endometrial carcinoma was performed to evaluate clinical course, treatment, recurrence rate, and survival. METHODS: A list of patients with clinical and surgical stage II endometrial carcinoma was obtained through the tumor registry and from the pathology department from 1988 to 1996. Data were collected on all cases of patients with endometrial carcinoma meeting stage II criteria by FIGO surgical staging. Variables including stage, histology, grade, lymph vascular space invasion (LVI), type and extent of surgery, radiation type and amount, smoking, menstrual status, parity, and age were evaluated for their predictive ability of disease recurrence. Cox proportional hazard regression models were used to examine the potential predictors of time to relapse univariately and multivariately. RESULTS: Of patients identified, 65 underwent primary surgical staging. Only adenocarcinomas were included. Mean follow-up time was 4.7 years (range 0.2-9.6 years). Postoperative radiation was given to 85.7% of patients. There were 10 patients (15.4%) with recurrence of disease with a mean time to recurrence of 25 months. Five-year disease-specific survival was 93%. The only significant predictor of time to relapse was LVI (P = 0.002) in the multivariate analysis. CONCLUSION: This retrospective review suggests that primary surgery followed by postoperative radiation therapy gives excellent results in surgical stage II disease. LVI appears to be a strong predictor of disease recurrence regardless of postoperative radiation therapy. It is difficult to draw conclusions about the type and amount of radiation given because recurrence rate is so low; however, it is reasonable to continue adjuvant radiation especially in cases where LVI is identified.

Adenocarcinoma↗
PubMed1999

Quality of life in advanced ovarian cancer: identifying specific concerns.

PURPOSE: To identify issues affecting the quality of life (QoL) in women receiving palliative therapy for ovarian cancer. METHODS: Twenty women with advanced recurrent ovarian cancer were interviewed to establish what issues affect QoL. All patients were receiving palliative chemotherapy or other palliative therapy in the department of Gynecologic Oncology at the Massachusetts General Hospital, and were felt to have a life expectancy of 1 year or less by best clinical estimate. RESULTS: Twenty patients with an average age of 56.7 years participated. Psychosocial issues were more common than physical ones, and patients were more likely to mention issues that positively impact on QoL rather than those with a negative effect. Most patients noted that a sense of hope, enhanced appreciation for day to day life, and a strong support system had a significantly positive effect on QoL. Issues negatively impacting QoL included fear of their disease (90%) and concern for family and friends (100%), particularly children. Most common physical symptoms impacting QoL included fatigue (100%) and anorexia (55%). CONCLUSIONS: Little research has been done into QoL issues for ovarian cancer patients receiving palliative care. Available QoL studies tend to focus on the physical aspects of a disease or its treatment. This pilot study suggests that women with advanced, recurrent ovarian cancer feel that psychosocial issues play a greater role in determining QoL than do physical issues. Further QoL studies for these patients should include assessment of psychosocial realms. This information can then be used to design interventions to improve QoL.

Journal Article↗
PubMed1999

A Phase I study of continuous infusion doxorubicin and paclitaxel chemotherapy with granulocyte colony-stimulating factor for relapsed epithelial ovarian cancer.

A Phase I study of paclitaxel and doxorubicin administered as concurrent 96-h continuous i.v. infusion was performed to determine the maximum tolerated dose (MTD), principal toxicities, and pharmacokinetics of this combination in women with relapsed epithelial ovarian cancer. The paclitaxel dose was fixed at 100 mg/m2 (25 mg/m2/day for 4 days). The dose of doxorubicin was escalated from 30 mg/m2 (7.5 mg/m2/day for 4 days) in increments of 10 mg/m2 until dose-limiting toxicity was observed. All patients received granulocyte colony-stimulating factor 5 microg/kg/day prophylactically. Apparent steady-state plasma levels of both drugs were determined in the final cohort of patients treated at the MTD. A total of 17 patients received 52 cycles of therapy. The median age was 58 years, and all patients had previously received one to five different regimens (median, 2) of chemotherapy, including both platinum and paclitaxel. The treatment was tolerated well, with grade 1-2 nausea being the most frequent side effect (73% of cycles). Anemia, neutropenia, thrombocytopenia, and mucositis became dose limiting at the fourth dose level, defining the MTD of doxorubicin in this regimen as 50 mg/m2. There were four partial responses and one complete response in 15 evaluable patients. Apparent steady-state plasma concentrations (mean +/- SD) of paclitaxel and doxorubicin in the three patients treated at the MTD were 33.9 +/- 12.5 nM and 15.7 +/- 1.3 nM, respectively. Paclitaxel and doxorubicin by continuous infusion is a well-tolerated and active chemotherapy regimen for recurrent ovarian cancer.

Adult↗
PubMed1999

Human ovarian cancer, cell lines, and primary ascites cells express the human Mullerian inhibiting substance (MIS) type II receptor, bind, and are responsive to MIS.

Six human ovarian cancer cell lines and samples of ascites cells isolated from 27 patients with stage III or IV ovarian papillary serous cystadenocarcinoma were studied individually to test whether recombinant human Mullerian inhibiting substance (rhMIS) acts via its receptor. To do these experiments, we scaled up production of rhMIS and labeled it successfully with biotin for binding studies, cloned the human MIS type II receptor for mRNA detection, and raised antibodies to an extracellular domain peptide for protein detection. These probes were first tested on the human ovarian cancer cell lines and then applied to primary ovarian ascites cells. rhMIS inhibited colony growth of five of six cell lines that expressed the human MIS type II receptor mRNA by Northern analysis while not inhibiting receptor-negative COS cells. Flow cytometry performed on MIS-sensitive ovarian cancer cell lines demonstrated specific and saturable binding of rhMIS (Kd = 10.2 nM). Ascites cells from 15 of 27 or 56% of patients tested bound biotinylated MIS (MIS-biotin) and, of the 11 that grew in soft agarose, 9 of 11 or 82% showed statistically significant inhibition of colony formation. Of the 15 patients who bound biotinylated MIS, mRNA was available for analysis from 9, and 8 of 9 expressed MIS type II receptor mRNA by reverse transcription-PCR, showing a statistically significant correlation, compared with binding, by chi2 analysis (P = 0.025). Solid ovarian cancers were positive for the MIS type II receptor protein by immunohistochemical staining, which colocalized with staining for antibody to CA-125 (OC-125). Thus, the detection of the MIS type I receptor by flow cytometry may be a useful predictor of therapeutic response to MIS and may be a modality to rapidly choose patients with late-stage ovarian cancer for treatment with MIS.

Adult↗
PubMed1998

Recurrent psammocarcinoma of the peritoneum with complete response to tamoxifen therapy.

Psammocarcinoma is a rare type of serous carcinoma arising from the ovary or peritoneum, characterized by massive psammoma body formation, invasiveness, and low-grade cytological features. A case of primary peritoneal psammocarcinoma is presented. Aspects of clinical presentation, diagnosis, and management are described. Emphasis is placed on successful management of recurrent disease using tamoxifen therapy.

Antineoplastic Agents, Hormonal↗
PubMed1997

Stage IB and IIA cervical cancer with negative lymph nodes: the role of adjuvant radiotherapy after radical hysterectomy.

The records of 171 patients with lymph node-negative stage IB and IIA cervical cancer primarily treated with radical hysterectomy and pelvic lymphadenectomy from 1974 to 1992 were retrospectively reviewed to identify poor prognostic factors and evaluate the role of adjuvant pelvic radiotherapy. One hundred sixteen patients (68%) were treated with radical hysterectomy alone (RH) and 55 patients (32%) received adjuvant radiotherapy (RH + RT). Factors predictive of recurrence for the entire group of patients included lymph-vascular space invasion (LVSI) (P = 0.003) and grade 3 histology (P = 0.04). Patients receiving RH + RT were older and more likely to have outer third cervical wall invasion, LVSI, positive margins, > or =2 cm pathologic tumor size, and >4 cm clinical tumor size (all P < 0.05). Overall, 28 patients (16%) developed recurrent disease with no difference between RH and RH + RT groups. After controlling for confounding variables, patients with LVSI who received RH + RT were less likely to develop disease recurrence than patients receiving RH alone (P = 0.04). LVSI is an important prognostic variable in lymph node-negative stage IB and IIA cervical cancer. Although adjuvant pelvic radiotherapy may decrease the risk of recurrence in patients with LVSI, the majority of patients with negative lymph nodes may be treated with radical surgery alone.

Adult↗