Cervical cancer radiation therapy compliance rates based on location of radiation therapy.

OBJECTIVE: Completion of radiation therapy (RT) within 60 days has been proposed as a national quality measure for patients with carcinoma of the cervix as protracted RT has been associated with worse oncologic outcomes. The objective of this study was to compare compliance rates based on location of RT administration. METHODS: This was a retrospective chart review of patients diagnosed with cervical cancer between January of 2000 to December of 2016 who were planned to undergo primary treatment with sensitizing chemotherapy and RT. Patients who completed both external beam radiation therapy (EBRT) and brachytherapy (BT) at the primary institution were compared to patients who completed a portion or all of their RT elsewhere. The primary outcome measured was completion of RT within 60 days. Secondary outcomes included compliance with sensitizing chemotherapy, total radiation dose, recurrence rate, progression free survival (PFS) and overall survival (OS). The groups were compared using standard statistical analysis. RESULTS: This study included 100 patients, 75 of which received all of their RT at the primary institution. These patients were more likely to complete RT within 60 days when compared to patients who underwent RT at different facilities (58.7% vs 24%, respectively; p = 0.005). Patients who underwent all of their RT at the primary institution completed their therapy an average of 16.4 days sooner (75.1 ±â€¯21.3 days versus 58.7 ±â€¯13.2 days; p = 0.001). Overall survival was significantly improved in this group (p = 0.03). CONCLUSION: Women who complete EBRT and BT at different institutions are more likely to have a protracted RT course (>60 days). These patients should be identified at diagnosis and efforts made to coordinate their care to avoid delays in treatment.

Outcomes of patients with low-risk endometrial cancer surgically staged without lymphadenectomy based on intra-operative evaluation.

OBJECTIVE: The objective of the study was to evaluate clinical outcomes in patients with stage I endometrial cancer undergoing surgical management without lymphadenectomy based on intra-operative assessment for low-risk disease. METHODS: Between 2000 and 2009, a total of 179 patients were surgically staged without lymphadenectomy for low-risk stage I endometrial cancer. Low-risk cancer was defined by intra-operative criteria based on both gross and frozen tissue microscopic evaluation: 1) G1 or G2 endometrioid histology; 2) myoinvasion <50%; 3) no cervical disease, and 4) no intra-abdominal metastasis. Records were reviewed for postoperative complications, pathological diagnoses, adjuvant radiation treatment, cancer recurrence, and mortality. RESULTS: Morbidity, cancer recurrence, and disease-specific mortality were low. Postoperative complications occurred in 5 patients (2.8%). Nine patients (5.0%) were offered adjuvant radiation for higher risk disease diagnosed on final pathology. Radiation morbidity was minimal: grade 1 vaginal toxicity in 2 patients. Three patients (1.7%) experienced recurrent cancer with mean time to recurrence of 43.7 months. Five year overall survival was 95.8%. The five year probability of disease-specific death was 1.1%. CONCLUSION: In an institution with reliable capability of pathological frozen tissue diagnosis, omission of lymph node dissection is a reasonable option in the surgical management of those patients with low-risk disease diagnosed by intra-operative factors.

A phase II evaluation of bortezomib in the treatment of recurrent platinum-sensitive ovarian or primary peritoneal cancer: a Gynecologic Oncology Group study.

OBJECTIVE: To determine the activity and pharmacodynamics (PD) of bortezomib in platinum-sensitive epithelial ovarian or primary peritoneal cancer (EOC/PPC). PATIENTS AND METHODS: Eligible women with recurrent EOC/PPC progressing between 6 and 12 months after initial chemotherapy were treated with bortezomib on days 1, 4, 8, and 11 [1.5 (cohort I) and 1.3 (cohort II) mg/m(2)/dose]. Patients must have had initial chemotherapy only. Response Evaluation Criteria in Solid Tumors (RECIST) was assessed by computed tomography (CT) scan every 2 cycles. 20S proteasome activity was quantified in three pre-treatment and a 1-hour post-treatment (cycle one, day 1) whole blood lysates. RESULTS: Initially, 26 evaluable patients were treated at the 1.5 mg/m(2)/dose level. Objective response rate was 3.8% (1/26), a partial response. An additional 10 patients (38.5%) had stable disease. Given concerns that treatment discontinuations due to toxicity limited drug exposure/activity a second cohort of 29 evaluable patients was accrued at 1.3 mg/m(2)/dose. The 1.3 mg/m(2)/dose regimen is currently approved as an indication for multiple myeloma and mantle cell lymphoma. Treatment was more tolerable, although objective responses remained low at 6.9% (2/29, partial responses). Second stage accrual was not warranted at either dose. Bortezomib effectively inhibited 20S proteasome activity in whole blood lysates between 37 and 92% in 24/25 (96%) patients in cohort I, and 14-84% in 27/28 (96%) patients in cohort II who provided satisfactory pre- and post-treatment specimens for testing. CONCLUSION: Bortezomib has minimal activity as a single-agent in the treatment of recurrent platinum-sensitive EOC/PPC. Treatment with bortezomib at 1.5 mg/m(2)/dose was not feasible in this patient population due to excess toxicity. Bortezomib was well tolerated at 1.3 mg/m(2)/dose.

Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients.

Endometrial cancer is the most common cancer in women with Lynch syndrome. The identification of individuals with Lynch syndrome is desirable because they can benefit from increased cancer surveillance. The purpose of this study was to determine the feasibility and desirability of molecular screening for Lynch syndrome in all endometrial cancer patients. Unselected endometrial cancer patients (N = 543) were studied. All tumors underwent microsatellite instability (MSI) testing. Patients with MSI-positive tumors underwent testing for germ line mutations in MLH1, MSH2, MSH6, and PMS2. Of 543 tumors studied, 118 (21.7%) were MSI positive (98 of 118 MSI high and 20 of 118 MSI low). All 118 patients with MSI-positive tumors had mutation testing, and nine of them had deleterious germ line mutations (one MLH1, three MSH2, and five MSH6). In addition, one case with an MSI-negative tumor had abnormal MSH6 immunohistochemical staining and was subsequently found to have a mutation in MSH6. Immunohistochemical staining was consistent with the mutation result in all seven truncating mutation-positive cases but was not consistent in two of the three missense mutation cases. We conclude that in central Ohio, at least 1.8% (95% confidence interval, 0.9-3.5%) of newly diagnosed endometrial cancer patients had Lynch syndrome. Seven of the 10 Lynch syndrome patients did not meet any published criteria for hereditary nonpolyposis colorectal cancer, and six of them were diagnosed at age >50. Studying all endometrial cancer patients for Lynch syndrome using a combination of MSI and immunohistochemistry for molecular prescreening followed by gene sequencing and deletion analysis is feasible and may be desirable.

Prevalence of illicit drug use in Asia and the Pacific.

This paper reports on the prevalence of drug use in Asia and the Pacific. It is based on the report "Situational analysis of illicit drug issues and responses in Asia and the Pacific", commissioned by the Australian National Council on Drugs Asia Pacific Drug Issues Committee. Review of existing estimates of the prevalence of people who use illicit drugs from published and unpublished literature and information from key informants and regional institutions was undertaken for the period 1998 - 2004. Estimates of the prevalence of people who use illicit drugs were conducted for 12 Asian and six Pacific Island countries. The estimated prevalence of those using illicit drugs ranges from less than 0.01% to 4.6%. Countries with estimated prevalence rates higher than 2% are Cambodia, Hong Kong, Philippines, Thailand, Indonesia, Laos and Malaysia. China, Myanmar and Vietnam have estimated prevalence rates ranging between less than 0.01% and 2%. Data to estimate prevalence rates was not available for Pacific Island countries and Brunei. Estimates of the prevalence of drug use are critical to policy development, planning responses and measuring the coverage of programs. However, reliable estimates of the numbers of people using illicit drugs are rare in Asia, particularly the Pacific.

Drug production, trafficking and trade in Asia and Pacific Island countries.

We report here on illicit drug production, trafficking and transit routes found in the Asia Pacific region. The report is based on the 'Situational analysis of illicit drug issues and responses in Asia and the Pacific', commissioned by the Australian National Council on Drugs Asia Pacific Drug Issues Committee. The situational analysis was a comprehensive desk based review; data sources included published and unpublished literature and key informant reports. It was found that Myanmar was the main producer of opium, heroin and amphetamine-type stimulants (ATS) in the Asia-Pacific region. China is now considered a major producer of methamphetamines, but other Asia-Pacific nations are also involved in production. Cannabis production was found throughout most of the Asia-Pacific region, in particular Cambodia and the Philippines. Drug trafficking and transit routes of Asia and the Pacific were proliferating and dynamic. The Pacific is mainly known as a trans-shipment point for drugs entering other countries in the region. Drug cultivation and production in Asia is substantial. The expansion of ATS production in the Asia Pacific region is causing much concern. Most drug traffickers change routes and tactics to exploit available vulnerable points along international borders. Responding effectively to the complexity and scale of drug production and trafficking in the Asia-Pacific region will remain a major challenge.

Illicit drug use and responses in six Pacific Island countries.

We report here on the illicit drug situation in six Pacific nations: Fiji, Papua New Guinea, Samoa, Solomon Islands, Tonga and Vanuatu. The report is based on the 'Situational analysis of illicit drug issues and responses in Asia and the Pacific', commissioned by the Australian National Council on Drugs Asia Pacific Drug Issues Committee. The situational analysis was a comprehensive desk-based review; data sources included published and unpublished literature and information from key informants. A range of psychoactive substances have been used traditionally across the Pacific region. Cannabis is the by far the most common and widespread illicit drug used in the six Pacific Islands reviewed. Drugs such as heroin, methamphetamines and cocaine are not used commonly due to their high cost compared to the average income. Currently, there is no overall regional or country-based illicit drug policy for the Pacific and few treatment programs; limited data exist to aid in understanding illicit drug use and the harms associated with its use in the Pacific. This review highlights the urgent need for strategic alcohol and drug research in the Pacific as a foundation for the development of policy.

Phase II trial of the pegylated liposomal doxorubicin in previously treated metastatic endometrial cancer: a Gynecologic Oncology Group study.

PURPOSE: To determine whether pegylated liposomal doxorubicin (PLD) has antitumor activity in pretreated patients with persistent or recurrent endometrial carcinoma and to define the nature and degree of toxicity of PLD. PATIENTS AND METHODS: Women with histologically documented recurrent or persistent measurable endometrial carcinoma and with failure of one prior treatment regardless of prior anthracycline therapy were enrolled. PLD was administered intravenously over a 1-hour period at a dose of 50 mg/m(2) every 4 weeks; the dosage was modified in accordance with observed toxicity. RESULTS: Of 46 patients entered, 42 were assessable for response, as three were declared ineligible on central pathology review and one was not assessable for response. Forty had received prior chemotherapy, 11 hormonal therapy, and 29 radiation therapy. Doxorubicin had been given to 32 patients, carboplatin with paclitaxel to six, carboplatin to one, and fluorouracil to one. Four patients had partial responses lasting 1.1, 2.1, 3.3, and 5.4 months; the overall response rate was 9.5% (95% confidence interval, 2.7% to 22.6%). Three of these responses (in liver and in lymph node) occurred in patients who had progressed after doxorubicin with either paclitaxel or cisplatin. The median number of courses was 2.5 (range, one to 14). Toxicity was generally mild: only 25 patients experienced leukopenia, with a median WBC count of 2,900 (range, 800 to 3,900) at nadir. The only grade 4 toxicities were one episode each of esophagitis, hematuria, and vomiting. The median overall survival was 8.2 months. CONCLUSION: PLD has only limited activity in pretreated advanced, recurrent endometrial cancer, but further trials in anthracycline-naive patients and in previously untreated patients are ongoing. Its toxicity profile should permit its use in combination with myelosuppressive drugs.

Randomized phase III trial of standard timed doxorubicin plus cisplatin versus circadian timed doxorubicin plus cisplatin in stage III and IV or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study.

PURPOSE: To determine if circadian timed (CT) chemotherapy results in improved response, progression-free survival (PFS), overall survival (OS), and lower toxicity, when compared with standard timed (ST) chemotherapy. MATERIALS AND METHODS: Eligibility criteria were stage III, IV, or recurrent endometrial cancer with poor potential for cure by radiation therapy or surgery; measurable disease; and no prior chemotherapy. Therapy was randomized to schedules of ST doxorubicin 60 mg/m2 plus cisplatin 60 mg/m2, or CT doxorubicin 60 mg/m2 at 6:00 am plus cisplatin 60 mg/m2 at 6:00 pm. Cycles were repeated every 3 weeks to a maximum of eight cycles. RESULTS: The ST arm included 169 patients, and the CT arm included 173 patients. The objective response rate (complete responses plus partial responses) was 46% in the ST group compared with 49% in the CT group (P =.26, one tail). Median PFS and OS were 6.5 and 11.2 months, respectively, in the ST group; and 5.9 and 13.2 months, respectively, in the CT group (PFS: P =.31; OS: P =.21, one tail). Median total doses were 209 mg/m2 doxorubicin and 349 mg/m2 cisplatin in the ST group, versus 246 mg/m2 doxorubicin and 354 mg/m2 cisplatin in the CT group. Grade 3 or 4 leukopenia occurred in 73% of patients in the ST arm and in 63% of patients in the CT arm. There were eight treatment-related deaths. CONCLUSION: In this trial, no significant benefit in terms of response rate, PFS or OS, or toxicity profile was observed with CT doxorubicin plus cisplatin in patients with advanced or recurrent endometrial carcinoma.

Phase III trial of doxorubicin plus cisplatin with or without paclitaxel plus filgrastim in advanced endometrial carcinoma: a Gynecologic Oncology Group Study.

PURPOSE: To determine whether the addition of paclitaxel to doxorubicin plus cisplatin improves overall survival (OS) in women with advanced or recurrent endometrial carcinoma. Secondary comparisons included progression-free survival (PFS), response rate (RR), and toxicities. PATIENTS AND METHODS: Eligible, consenting patients received doxorubicin 60 mg/m(2) and cisplatin 50 mg/m(2) (AP), or doxorubicin 45 mg/m(2) and cisplatin 50 mg/m(2) (day 1), followed by paclitaxel 160 mg/m(2) (day 2) with filgrastim support (TAP). The initial doxorubicin dose in the AP arm was reduced to 45 mg/m(2) in patients with prior pelvic radiotherapy and those older than 65 years. Both regimens were repeated every 3 weeks to a maximum of seven cycles. Patients completed a neurotoxicity questionnaire before each cycle. RESULTS: Two hundred seventy-three women (10 ineligible) were registered. Objective response (57% v 34%; P <.01), PFS (median, 8.3 v 5.3 months; P <.01), and OS (median, 15.3 v 12.3 months; P =.037) were improved with TAP. Treatment was hematologically well tolerated, with only 2% of patients receiving AP, and 3% of patients receiving TAP experiencing neutropenic fever. Neurologic toxicity was worse for those receiving TAP, with 12% grade 3, and 27% grade 2 peripheral neuropathy, compared with 1% and 4%, respectively, in those receiving AP. Patient-reported neurotoxicity was significantly higher in the TAP arm following two cycles of therapy. CONCLUSION: TAP significantly improves RR, PFS, and OS compared with AP. Evaluation of this regimen in the high-risk adjuvant setting is warranted, but close attention should be paid to the increased risk of peripheral neuropathy.

Goserelin acetate as treatment for recurrent endometrial carcinoma: a Gynecologic Oncology Group study.

This Gynecologic Oncology Group (GOG) study was designed to estimate the activity of goserelin acetate as treatment for advanced and recurrent endometrial carcinoma. Forty evaluable patients received monthly treatment with goserelin acetate at a dose of 3.6 mg, given subcutaneously. Standard GOG response and adverse effects criteria were used. The median age of patients was 71 years. Seventy-one percent of patients had received prior radiation therapy; 18% of patients were reported to have received prior progestational therapy for endometrial cancer. One patient had received prior chemotherapy. There were two complete responses (5%) and three partial responses (7%). One response occurred in a patient who previously did not respond to progestin therapy after having achieved a response. The overall response rate was 11% (95% CI: 4-27%). Median progression-free survival was 1.9 months and median overall survival was 7.3 months. No severe or life-threatening toxicities occurred because of goserelin. Deep venous thrombosis developed in two patients. This study confirmed the limited activity of goserelin acetate in endometrial carcinoma, with only one response in a patient previously treated with hormonal therapy. The activity is insufficient to warrant further study of the single agent at this time. Elucidation of the mechanism of action of this drug may allow more effective use in conjunction with other agents in the future.

The long winding road of opioid substitution therapy implementation in South-East Asia: challenges to scale up.

The South-East Asia Region contains an estimated 400,000-500,000 people who inject drugs (PWID). HIV prevalence among PWID is commonly 20% or higher in Indonesia, Thailand, Myanmar and some regions of India. Opioid substitution therapy (OST) is an important HIV prevention intervention in this part of the world. However, key challenges and barriers to scale up of OST exist, including: pervasive stigma and discrimination towards PWID; criminalisation of drug use overshadowing a public health response; lack of political will and national commitment; low financial investment; focus towards traditional treatment models of detoxification and rehabilitation; inadequate dosing of OST; and poor monitoring and evaluation of programmes. Our review of local evidence highlights that OST can be successful within the Asian context. Such evidence should be utilised more widely to advocate for policy change and increased political commitment to ensure OST reaches substantially more drug users. Significance for public healthSeveral countries in the World Health Organization South-East Asia Region can be commended for introducing opioid substitution therapy (OST) to address the ongoing HIV epidemic among people who inject drugs (PWID). Local evidence shows OST is an effective drug treatment approach in the Asian context given sufficient technical and institutional support. However, despite much progress, the number of OST dispensing sites and recipients remains totally inadequate in terms of impact upon the current HIV epidemic among PWID. Ongoing advocacy is needed if countries are to achieve the WHO's target of 40% of PWID being dosed with OST. Greater political commitment a strengthened policy environment, capacity building for OST clinics, lessening the criminalisation of drug use and promoting a public health response will give many more PWID access to OST and slow the advance of the HIV epidemic.

Advocacy for harm reduction in China: a new era dawns.

BACKGROUND: China's initial response to drug use and HIV was largely ineffective but has improved with recent government endorsement of harm reduction interventions. This paper examines the views of senior key informants inside China who articulated core needs and objectives for the development of a harm reduction advocacy strategy. METHODS: Thirty-nine key informants (KI) were interviewed, representing 19 stakeholder bodies selected from the Chinese government public health sector, public security sector, international agencies such as WHO, UNODC and UNAIDS, and international non-government organisations. RESULTS: The concept of harm reduction is widely understood and considered valid. Support for harm reduction is increasing, but KIs perceived an imbalance between the rapid expansion of methadone maintenance treatment programs over needle and syringe programs and other interventions. Challenges for harm reduction identified by KIs included: policy inconsistencies; lack of skilled resources, training programs and technical capacity; poor coverage of interventions; and gaps in the sharing of information. KIs suggested numerous ways to strengthen the capacity of the government and communities to reduce drug related harm. DISCUSSION: Increased acceptance of harm reduction in China, particularly among public security, implies a new level of optimism towards addressing the HIV epidemic among drug users, and parallels an impressive expansion of harm reduction interventions. Nevertheless, scaling up a response to the ongoing dual epidemic of drug use and HIV remains an enormous challenge. With appropriate technical education and training, ongoing advocacy, and a cohesive, coordinated multi-sectoral effort, the capacity of the government and community to adopt, support and promote measures to reduce HIV and other drug related harm would be markedly strengthened.

Examining HIV, drug use and risk behaviours: A case study in the custodial settings of Thailand and Indonesia.

Custodial settings are high-risk environments for HIV. This paper examines publicly available data about the drug use and risk behaviours of Thai and Indonesian prisoners and outlines a process used to collect new data. In 2005, the Departments of Corrections in Thailand and Indonesia requested researchers examine HIV and drug use issues but the findings are too sensitive to publish. The Departments of Corrections in Thailand and Indonesia are using the results to develop public health responses.

Are prediction models for Lynch syndrome valid for probands with endometrial cancer?

Currently, three prediction models are used to predict a patient's risk of having Lynch syndrome (LS). These models have been validated in probands with colorectal cancer (CRC), but not in probands presenting with endometrial cancer (EMC). Thus, the aim was to determine the performance of these prediction models in women with LS presenting with EMC. Probands with EMC and LS were identified. Personal and family history was entered into three prediction models, PREMM(1,2), MMRpro, and MMRpredict. Probabilities of mutations in the mismatch repair genes were recorded. Accurate prediction was defined as a model predicting at least a 5% chance of a proband carrying a mutation. From 562 patients prospectively enrolled in a clinical trial of patients with EMC, 13 (2.2%) were shown to have LS. Nine patients had a mutation in MSH6, three in MSH2, and one in MLH1. MMRpro predicted that 3 of 9 patients with an MSH6, 3 of 3 with an MSH2, and 1 of 1 patient with an MLH1 mutation could have LS. For MMRpredict, EMC coded as "proximal CRC" predicted 5 of 5, and as "distal CRC" three of five. PREMM(1,2) predicted that 4 of 4 with an MLH1 or MSH2 could have LS. Prediction of LS in probands presenting with EMC using current models for probands with CRC works reasonably well. Further studies are needed to develop models that include questions specific to patients with EMC with a greater age range, as well as placing increased emphasis on prediction of LS in probands with MSH6 mutations.

Harm reduction programmes in the Asia--Pacific Region.

INTRODUCTION AND AIMS: This paper reports on the public health intervention of harm reduction to address drug use issues in the Asia-Pacific region. DESIGN AND METHODS: It is based on the report 'Situational analysis of illicit drug issues and responses in Asia and the Pacific', commissioned by the Australian National Council on Drugs Asia Pacific Drug Issues Committee. A comprehensive desk-based review based on published and unpublished literature and key informant data. RESULTS: Drug use in the Asia--Pacific region is widespread, resulting in serious adverse health consequences. Needle and syringe programmes are found in some parts of Asia, but not in the six Pacific Island countries reviewed. Outreach and peer education programmes are implemented, but overall appear minor in size and scope. Substitution therapy programmes appear to be entering a new era of acceptance in some parts of Asia. Primary health care specifically for drug users overall is limited. DISCUSSION AND CONCLUSIONS: Harm reduction programmes in the Asia--Pacific region are either small in scale or do not exist. Most programmes lack the technical capacity, human resources and a limited scope of operations to respond effectively to the needs of drug users. Governments in this region should be encouraged to endorse evidence-based harm reduction programmes.

Selling syringes to injecting drug users: a study of five pharmacies in Hanoi, Vietnam.

BACKGROUND: HIV continues to spread rapidly throughout Vietnam with injection drug use remaining the main risk factor for infection. The extent of pharmacy-based needle and syringe distribution has not previously been measured in Vietnam; this article reports on a pilot study exploring pharmacy-based harm reduction activities in Vietnam's capital, Hanoi. METHODOLOGY: Five pharmacies located in Dong Da and Thanh Xuan districts in Hanoi, where two peer-based needle and syringe programs (NSPs) also operate, recorded the numbers of syringes sold to injecting drug users (IDUs) over a one-week period. Each pharmacist participated in a semi-structured interview aimed at understanding the pharmacists' views of syringe distribution and HIV prevention. RESULTS: The five pharmacies sold an average of 93 syringes per pharmacy to IDUs during the study week. Pharmacists demonstrated a solid understanding of HIV transmission risk factors and a strong commitment to continuing HIV prevention activities. CONCLUSIONS: Our data are based on few observations and are very preliminary, but suggest that pharmacies contribute a significant proportion of the total syringe supply to IDUs in Hanoi. Given adequate support, pharmacies could be an effective vehicle for scaling up harm reduction services in Hanoi and throughout Vietnam.

Malaysia and harm reduction: the challenges and responses.

In Malaysia the response to illicit drug use has been largely punitive with the current goal of the Malaysian government being to achieve a drug-free society by 2015. This paper outlines the results of a desk-based situation assessment conducted over a 3-week period in 2004. Additional events, examined in 2005, were also included to describe more recent policy developments and examine how these came about. Despite punitive drug policy there has been a substantial rise in the number of drug users in the country. Over two-thirds of HIV/AIDS cases are among injecting drug users (IDUs) and there has been an exponential rise in the number of cases reported. Further, data suggest high risk drug use practices are widespread. Harm reduction initiatives have only recently been introduced in Malaysia. The successful piloting of substitution therapies, in particular methadone and buprenorphine, is cause for genuine hope for the rapid development of such interventions. In 2005 the government announced it will allow methadone maintenance programmes to operate beyond the pilot phase and needle and syringe exchange programmes will be established to serve the needs of IDUs.

Phase II trial of liposomal doxorubicin at 40 mg/m(2) every 4 weeks in endometrial carcinoma: a Gynecologic Oncology Group Study.

OBJECTIVE: In patients with disseminated endometrial carcinoma, liposomal doxorubicin has possible advantages over doxorubicin which has proven single agent activity but well known cardiac toxicity. Before replacing doxorubicin in clinical trials, the Gynecologic Oncology Group (GOG) decided to conduct a phase II clinical trial of liposomal doxorubicin (Ortho Biotech Products L. P., Raritan, NJ) in first-line therapy of patients with disseminated endometrial carcinoma. METHODS: Patients with initial histologic confirmation of endometrial carcinoma presenting with disseminated or recurrent cancer who had not previously received cytotoxic drugs were considered for participation in this clinical trial. Eligible patients had measurable disease, GOG performance status 0-2, and adequate bone marrow, renal, and hepatic function according to standard criteria. Liposomal doxorubicin 40 mg/m(2) was given by intravenous injection on an every 4-week cycle until toxicity or progression. Patients who remained free from tumor progression or intolerable toxicity received at least one to a maximum of 20 cycles of liposomal doxorubicin. RESULTS: Fifty-six patients were registered, of whom three were determined ineligible (prior malignancy = 2, inadequate pathology material = 1). One patient never received therapy, leaving 52 evaluable patients. Two patients (3.8%) achieved a complete response, four (7.7%) exhibited a partial response, and 31 (59.7%) had stable disease. The most common adverse events were constitutional (32/52), anemia (28/52), pain (27/52), dermatologic (25/52), and cardiovascular (12/52). CONCLUSIONS: In this trial, liposomal doxorubicin had a response rate of 11.5% in first-line treatment of disseminated endometrial carcinoma when given at 40 mg/m(2) every 4 weeks. In view of the associated skin toxicity at this dose, liposomal doxorubicin does not appear to be a suitable replacement for the more active doxorubicin for therapy of endometrial carcinoma.