Long-term remission of clear cell carcinoma of the cervix after chemoradiation with 109 cycles of paclitaxel: a case report and literature review.

BACKGROUND: Clear cell carcinoma of cervix (CCCC) is a rare cervical neoplasm that is usually associated with diethylstilbestrol (DES) exposure in utero as a primary risk factor. Advanced stage disease typically has poor outcomes and no evidence-based approach exists to guide clinicians in treating this rare disease. CASE: The authors report a case of locally advanced CCCC in a 37-year-old Caucasian female. She underwent chemoradiation therapy that included 109 courses of paclitaxel chemotherapy until no disease could be detected on imaging studies. She is now disease-free 13 years after discontinuing chemotherapy. CONCLUSION: A prolonged course of single agent paclitaxel after completing standard radiation therapy was successful in achieving remission in a patient with this rare disease.

Phase I dose escalation of paclitaxel in patients with advanced ovarian cancer receiving cisplatin: rapid development of neurotoxicity is dose-limiting.

PURPOSE: To determine the maximum-tolerable dose (MTD) of paclitaxel in a phase I dose-escalation study when combined with cisplatin in patients with advanced ovarian cancer receiving filgrastim for prophylaxis of myelosuppression. PATIENTS AND METHODS: A total of 23 patients with stage II (bulky residual), III, or IV epithelial ovarian cancer were treated (following debulking surgery) with paclitaxel as a 3-hour infusion followed by cisplatin (75 mg/m2) administered over 4 hours on day 1, repeated every 21 days for six cycles. Filgrastim (5 micrograms/kg/d) was administered subcutaneously (SC) beginning on day 2 of each cycle through neutrophil recovery (absolute neutrophil count [ANC] > 10,000/microL). Patients were assigned to one of six escalating dose levels of paclitaxel: 150 (n = 3), 175 (n = 3), 200 (n = 3), 225 (n = 4), 250 (n = 4), and 275 mg/m2 (n = 6). RESULTS: At each paclitaxel dose level (150, 175, 200, 225, 250, and 275 mg/m2), the numbers of patients who completed six cycles without dose reduction were three (100%), three (100%), two (66%), two (50%), three (75%), and zero (0%), respectively. The numbers of patients who experienced a grade III/IV adverse event (hematologic or nonhematologic) were zero (0%), two (66%), two (66%), one (25%), four (100%), and five (80%), respectively. Reasons for dose reduction included neurotoxicity (225 mg/m2, n = 1; 275 mg/m2, n = 2), neutropenia (225 mg/m2, n = 2), diarrhea (275 mg/m2, n = 2), and nephrotoxicity (225 mg/m2, n = 1). Reasons for not completing six cycles at full or reduced dose included neuropathy (200, 225, and 275 mg/m2, n = 1 each) physician request (275 mg/m2, n = 1), and death (275 mg/m2, n = 1). Hematopoietic toxicity was minimal. Six patients developed grade III/IV neutropenia. No patient developed thrombocytopenia below a level of 50,000/microL. CONCLUSION: The MTD of paclitaxel was determined to be 225 mg/m2 when administered as a 3-hour infusion and combined with cisplatin (75 mg/m2). Nonhematologic dose-limiting toxicities were neuropathy and diarrhea. The neuropathy often had a rapid onset, especially at the higher dose levels.

Recurrent epithelial ovarian carcinoma: a randomized phase III study of pegylated liposomal doxorubicin versus topotecan.

PURPOSE: To compare the efficacy and safety of pegylated liposomal doxorubicin (PLD) and topotecan in patients with epithelial ovarian carcinoma that recurred after or didn't respond to first-line, platinum-based chemotherapy. PATIENTS AND METHODS: Patients with measurable and assessable disease were randomized to receive either PLD 50 mg/m(2) as a 1-hour infusion every 4 weeks or topotecan 1.5 mg/m(2)/d for 5 consecutive days every 3 weeks. Patients were stratified prospectively for platinum sensitivity and for the presence or absence of bulky disease. RESULTS: A total of 474 patients were treated (239 PLD and 235 topotecan). They comprised the intent-to-treat population. The overall progression-free survival rates were similar between the two arms (P =.095). The overall response rates for PLD and topotecan were 19.7% and 17.0%, respectively (P =.390). Median overall survival times were 60 weeks for PLD and 56.7 weeks for topotecan. Data analyzed in platinum-sensitive patients demonstrated a statistically significant benefit from PLD for progression-free survival (P =.037), with medians of 28.9 for PLD versus 23.3 weeks for topotecan. For overall survival, PLD was significantly superior to topotecan (P =.008), with a median of 108 weeks versus 71.1 weeks. The platinum-refractory subgroup demonstrated a nonstatistically significant survival trend in favor of topotecan (P =.455). Severe hematologic toxicity was more common with topotecan and was more likely to be associated with dosage modification, or growth factor or blood product utilization. CONCLUSION: The comparable efficacy, favorable safety profile, and convenient dosing support the role of PLD as a valuable treatment option in this patient population.

Phase II study of liposomal doxorubicin in platinum- and paclitaxel-refractory epithelial ovarian cancer.

PURPOSE: Stealth liposomal doxorubicin (Alzal Corp, Palo Alto, CA) has a slower clearance rate than free doxorubicin, resulting in sustained serum levels. Liposomal encapsulation also leads to increased concentration of drug in tumor tissue. Meta-analysis of previous studies has shown that doxorubicin has activity in epithelial ovarian cancer. The current study was developed to examine the activity of Stealth liposomal doxorubicin in platinum- and paclitaxel-refractory ovarian cancer. PATIENTS AND METHODS: Patients had epithelial ovarian cancer that either progressed on or recurred within 6 months of completion of platinum and paclitaxel chemotherapy. All patients had measurable disease. Stealth liposomal doxorubicin was administered at 50 mg/m(2) every 4 weeks as a 1-hour infusion. RESULTS: Eighty-nine patients were treated and included in an intent-to-treat analysis. There were 82 patients who were platinum and paclitaxel refractory and met all study criteria. There was one complete response and 14 partial responses, for a total response rate of 16.9% (95% confidence interval [CI], 9.1% to 24.6%). For platinum- and paclitaxel-refractory patients, the response rate was 18.3% (95% CI, 9.9% to 26.7%). Median time to progression was 19. 3 weeks for the entire population. Ten patients (11.2%) withdrew because of adverse events related to the drug (palmar-plantar erythrodysesthesia [PPE], n = 3; asthenia, n = 2; cardiac, n = 2; neutropenia, n = 1; stomatitis, n = 1; and edema, n = 1). There were no drug-related fatal events. There were only eight grade 4 adverse events attributable to the drug. Stomatitis, PPE, and skin lesions were managed with dose reductions and delays in most cases. CONCLUSION: Stealth liposomal doxorubicin has activity in refractory epithelial ovarian cancer. PPE and stomatitis can usually be managed by dose adjustment. The ease of administration makes this an attractive agent.

Squamous carcinoma of the cervix complicating pregnancy: recurrence in episiotomy after vaginal delivery.

A patient developed recurrence of squamous carcinoma of the cervix in the episiotomy scar after vaginal delivery through the involved cervix. At the time of her radical hysterectomy, all margins and nodes were free of tumor, suggesting implantation at delivery as the etiology of the recurrence. Review of the literature revealed three other cases of episiotomy recurrence. All cases were either clinically unsuspected or had negative Papanicolaou tests during pregnancy. Careful surveillance and early therapy appear to give a more favorable prognosis for this unusual type of recurrence.

High-risk metastatic gestational trophoblastic disease.

The clinical course of 61 patients with high-risk metastatic gestational trophoblastic disease was reviewed. Currently, 34 patients (56%) are alive and in complete remission. The survival rate after full-term pregnancy was significantly worse than after any other type of antecedent pregnancy. Analyzing survival by individual high-risk criteria revealed significantly improved survival for those patients with elevated beta-human chorionic gonadotropin titer alone when compared with all other high-risk criteria. Fifty-eight percent of patients (14 of 24) primarily treated with alternating-sequential therapy consisting of methotrexate and actinomycin-D experienced a complete remission. Of those patients primarily treated with methotrexate, actinomycin-D, and cyclophosphamide, 63% (20 of 32) achieved a complete remission. Treatment with second-line chemotherapy was largely unsuccessful. Aggressive early treatment is warranted in this group of patients, using multiagent chemotherapy. A search for newer more effective regimens should continue.

Self-instruction to prevent HIV infection among African-American and Hispanic-American adolescents.

This study tested the efficacy of self-instruction intervention to reduce avoidable risks for HIV infection associated with drug use and unsafe sexual activity among African-American and Hispanic adolescents (N = 60). After completing pretests, adolescent participants in the study were randomly divided into three conditions. Participants in one condition received a self-instructional guide about AIDS and its transmission along with group instruction in using the guide. Adolescents in another condition received the guide without group instruction. Participants in the third condition received neither the guide nor group instruction. Outcome findings indicate that participants in the two self-instruction conditions improved more between pretest and posttest assessments on measures of HIV infection risk compared with adolescents in the control condition.

African-American and Hispanic-American adolescents, HIV infection, and preventive intervention.

This paper considers strategies for preventing human immunodeficiency virus (HIV) infection among African-American and Hispanic-American adolescents. We describe culturally sensitive interventions based on social learning theory. The interventions combine elements of cognitive-behavioral skills for problem solving, coping, and interpersonal communication with elements of ethnic pride and HIV facts. The paper discusses the strengths and limitations of skills intervention for AIDS prevention and concludes with directions for research.

Transabdominal and transvaginal sonography of pelvic masses.

Determination of the type of pelvic mass by pelvic sonography was improved significantly when a transvaginal study was performed after transabdominal sonography. Of 34 patients who underwent both studies, transvaginal sonography (TVS) was considered to add diagnostic information in 24 (70%); transabdominal sonography (TAS) was better than TVS in 4 (12%); TVS was equivalent to TAS in 5 (15%), and neither were accurate in 1 (3%). It is concluded that the use of transvaginal sonography as an adjunct to TAS is warranted for evaluating most pelvic masses; especially those confined to the true pelvis.

A phase I/II dose escalation study of carboplatin in the treatment of newly diagnosed patients with advanced ovarian cancer receiving paclitaxel.

The objective of this study was to determine the maximum tolerated dose of carboplatin when administered with paclitaxel in previously untreated patients with ovarian cancer. Patients were treated with paclitaxel at 225 mg/m2 for 3 hours followed by carboplatin at an area under the curve (AUC) of 6, 7, 8, or 9 every 3 weeks. Granulocyte colony-stimulating factor was added if needed to maintain dose intensity before dose reductions were used for grade 4 hematologic toxicity or febrile neutropenia. Twenty-two patients were enrolled in the study. At the AUC 6 level, five of six patients finished all six cycles. At the AUC 7 level, four of five patients completed six cycles, although three required dose reductions for toxicity. At the AUC 8 level, all four patients completed six cycles and two required dose reductions. The AUC 9 level was not well tolerated. Only four of seven patients completed six cycles. Neutropenia was common, and transient thrombocytopenia was more severe and required dose reduction, especially in later cycles. An AUC of 8 is the maximum tolerated dose of carboplatin in combination with paclitaxel at 225 mg/m2 for 3 hours.

Hapalotrema (Digenea: Spirorchidae) in the green turtle (Chelonia mydas) in Australia.

Hapalotrema mehrai Rao, 1976 and Hapalotrema postorchis Rao, 1976 (Digenea: Spirorchidae) are redescribed from the heart and pulmonary arteries of the green turtle, Chelonia mydas, from Moreton Bay in south-eastern Queensland. Hapalotrema pambanensis Gupta and Mehrotra, 1981 from C. mydas in India is made a synonym of H. mehrai. Hapalotrema dorsopora Dailey, Fast and Balazs, 1993 from C. mydas from Hawaii was described with a dorsally opening uterine pore, but this is found to be the opening of Laurer's canal; therefore H. dorsopora is also made a synonym of H. mehrai. In addition to differences in the numbers of testes and general dimensions, H. mehrai and H. postorchis differ in the development of Laurer's canal and in the absence of a canalicular seminal receptacle in H. postorchis.

Sigmoidovaginal fistula secondary to diverticular disease. A report of three cases.

Colovaginal fistula from any cause is rare. Diverticular disease is the most common cause. We treated three women for sigmoidovaginal fistulae secondary to diverticular disease. These 3 cases bring the total number reported to 49. Diagnosis of these fistulae may be difficult, and controversy exists over which form of surgical management should be employed. Since more women are living to an age at which diverticular disease is common, colovaginal fistulae probably will be encountered by the gynecologist with increasing frequency. Colovaginal fistula secondary to diverticular disease should be considered in the differential diagnosis when an elderly women complains of flatus vaginalis.

Multi-agent chemotherapy in combination with fractioned radiation therapy for advanced carcinoma of the cervix: acute toxicity.

Five patients with advanced, previously untreated squamous cell carcinoma of the cervix were treated with combination chemotherapy (cisplatin, mitomycin C, and bleomycin) while undergoing daily fractioned radiation therapy to cover all known disease. All patients exhibited complete clinical responses at the time of the completion of external radiation therapy. Toxicities encountered were mild. This regimen deserves further study in patients with advanced squamous cell carcinoma of the cervix.

Epizootic mortality of free-living green turtles, Chelonia mydas, due to coccidiosis.

At least 70 wild green sea turtles, Chelonia mydas, died in the Moreton Bay area of southeast Queensland, Australia over 6 wk in spring 1991. Based on the necropsy of 24 turtles, there was a severe enteritis or encephalitis associated with Caryospora cheloniae, a coccidial pathogen previously recorded only in farm-reared Ch. mydas hatchlings. Infection was characterized by the presence of coccidia in extra-intestinal lesions. Oocysts were observed to sporulate, after which sporozoites escaped into seawater to form a novel stellate configuration. We conclude that C. cheloniae is pathogenic for life stages other than hatchling Ch. mydas and that naturally-occurring coccidiosis is a significant disease of free-living Ch. mydas.

An outbreak of malignant catarrhal fever in young rusa deer (Cervus timorensis).

On the basis of clinical signs and histological findings eight 9-month-old male rusa deer (Cervus timorensis) were diagnosed with sheep associated-malignant catarrhal fever. Following a variable course involving rectal temperatures around 40.5 degrees C, depression, inappetence, diarrhoea, corneal opacity and hypopyon all animals died or were euthanased over a 5-week period. Severe multifocal vasculitis, mainly periglomerular and in the arcuate vessels were consistent histological findings which in the past have been adequate to confirm clinical diagnosis of sheep associated-malignant catarrhal fever. A nested polymerase chain reaction test has been used to detect a sheep associated-malignant catarrhal fever PRC product, 238 base-pairs in size, in DNA extracted from lymphocyte preparations. The result supported the diagnosis of sheep associated-malignant catarrhal fever in these deer.

Suicide by poisoning.

An epidemiological evaluation was conducted on 270 patients who died at the General Hospital, Port-of-Spain after presenting with deliberate self-poisoning between January, 1986 and June, 1990. The cause of death was confirmed by autopsy and toxicological analysis. Epidemiological variables of age, sex, race, precipitating factors and types of poison used were assessed. It was found that the male to female ratio was 2.7:1. East Indians accounted for 54.4%, Africans 42.0%, people of mixed ethnic origin 3% and Caucasians 0.6%. The majority of cases (52.6%) were seen in the age group 11-34 years. "Lovers' quarrels" (35.4% of cases), psychiatric illness (27.8% of cases) and family disputes (27% of cases) were reported as the most frequent precipitating events in suicide. East Indians predominated in those suicides precipitated by "lovers' quarrels" and family disputes, accounting for 63.2% and 58.9% of these cases, respectively; while for those suicides in which psychiatric illnesses were the main precipitating event. Africans were represented by 53.3% and East Indians 45.3%. Depression was the most common psychiatric illness diagnosed. Paraquat was the most popular poison used in 63.7% of the suicidal cases, and other agrochemicals were used in 20% of cases.

Systemic toxoplasmosis in captive flying-foxes.

Systemic toxoplasmosis caused by Toxoplasma gondii was diagnosed in two juvenile, captive flying-foxes (Pteropus conspicillatus and P. scapulatus), which died following respiratory distress. One animal displayed clinical signs suggestive of neurological disease. This is the first report of this disease in megachiropteran bats and adds to the list of differential diagnoses for both systemic and neurological disease in these animals. The role of captivity in the exposure and development of the disease is discussed.

Efficacy and safety of erlotinib HCl, an epidermal growth factor receptor (HER1/EGFR) tyrosine kinase inhibitor, in patients with advanced ovarian carcinoma: results from a phase II multicenter study.

The aim of this single-arm, phase II study was to estimate the tumor response rate and safety profile of erlotinib HCl (erlotinib, Tarceva, OSI-774) monotherapy in patients with refractory, recurrent, HER1/EGFR-positive epithelial ovarian tumors, who had failed prior taxane and/or platinum-based chemotherapy. Thirty-four patients received 150 mg erlotinib orally once daily for up to 48 weeks or until disease progression or dose-limiting toxicity. Two patients had partial responses, lasting 8+ and 17 weeks, giving an objective response rate of 6% (95% confidence interval [CI], 0.7-19.7%). Fifteen patients (44%) had stable disease, and 17 patients (50%) had progressive disease. Median overall survival was 8 months (95% CI, 5.7-12.7 months), with a 1-year survival rate of 35.3% (95% CI, 19.8-53.5%). Patients with rash survived significantly longer than those without (P= 0.009), correlating with rash grade. Erlotinib was generally well tolerated. The most frequent erlotinib-related adverse events were rash (68%) and diarrhea (38%). Erlotinib had marginal activity but was generally well tolerated. The safety profile appears more favorable than typically experienced with standard chemotherapeutic agents, which is encouraging in these heavily pretreated patients. Combination of erlotinib with chemotherapy or other targeted agents should be considered.