Comparison of pulsed actinomycin D and 5-day actinomycin D as first-line chemotherapy for low-risk gestational trophoblastic neoplasia.

OBJECTIVE: To compare the treatment outcome and cost-effectiveness of pulsed actinomycin D (Act-D) and 5-day Act-D in patients with low-risk gestational trophoblastic neoplasia (GTN). METHOD: The present retrospective study included patients with low-risk GTN who received pulsed Act-D or 5-day Act-D as first-line chemotherapy at West China Second Hospital, Chengdu, China, between January 1, 2016, and December 31, 2017. Complete remission rates, mean number of treatment courses, and adverse events were compared, and a cost-effectiveness analysis was performed. RESULTS: The study included 34 patients treated with pulsed Act-D and 26 patients treated with 5-day Act-D. Overall complete remission was observed in 21 (62%) patients in the pulsed Act-D group and 19 (73%) patients in the 5-day Act-D group (P=0.355); the mean number of treatment courses were 5.1 and 5.3, respectively (P=0.686). When Act-D failed, patients in each group required 4.9 and 4.6 courses, respectively, of a multi-agent regimen (P=0.545). No major adverse events were observed but moderate adverse events were more frequent in the pulsed Act-D group (P=0.011). The 5-day Act-D regimen was more expensive compared with pulsed Act-D regimen (US$7504.33 vs $5541.79), with an incremental cost-effectiveness ratio of $64 557.08 per avoidance of treatment failure. CONCLUSION: Pulsed Act-D was more cost-effective than 5-day Act-D and could be preferred when considering Act-D as chemotherapy for low-risk GTN.

Are different methotrexate regimens as first line therapy for low risk gestational trophoblastic neoplasia more cost effective than the dactinomycin regimen used in GOG 0174?

OBJECTIVES: Gynecologic Oncology Group (GOG) 0174 compared weekly intramuscular methotrexate (MTX) with biweekly pulsed intravenous dactinomycin (Act-D) as single-agent chemotherapy for low-risk gestational trophoblastic neoplasia (GTN). Act-D had a higher rate of initial complete response (CR) (70% vs. 53%, p=0.01), but multi-day regimens of MTX have higher historic success rates. We assessed the cost-effectiveness of Act-D vs. MTX per GOG 0174 and explored multi-day MTX regimens. METHODS: A cost effectiveness decision model was constructed with data from GOG 0174. Outcome was cost per first-line treatment success expressed in terms of incremental cost-effectiveness ratio (ICER). Front-line failures were assumed to receive cross-over single agent therapy, second line failures; multi-agent chemotherapy. GOG 0174 had no quality of life (QOL) evaluation, so equal QOL (utility 1.0) was assumed but varied in sensitivity analysis. A second exploratory model included 5-day and 8-day MTX regimens. RESULTS: Act-D ($18,505) was more expensive compared to weekly MTX ($8950) with an ICER of $56,215 per first-line treatment success compared to weekly MTX. Small decreases in QOL dramatically increased the ICER during sensitivity analysis. Models with multi-day MTX regimens were also more cost-effective than Act-D. If effectiveness was redefined as avoidance of multi-agent chemotherapy, weekly MTX was more effective. CONCLUSIONS: With a complete cure rate for low-risk GTN regardless of initial agent, our model supports provider hesitation toward first line Act-D for low risk GTN. While Act-D is more effective for first line treatment success, it is more costly, and does not decrease rate of multi-agent chemotherapy use.

Conservative strategy in infantile fibrosarcoma is possible: The European paediatric Soft tissue sarcoma Study Group experience.

BACKGROUND: Infantile fibrosarcoma (IFS) is a very rare disease occurring in young infants characterised by a high local aggressiveness but overall with a favourable survival. To try to reduce the total burden of therapy, the European pediatric Soft tissue sarcoma Study Group has developed conservative therapeutic recommendations according to initial resectability. MATERIAL AND METHODS: Between 2005 and 2012, children with localised IFS were prospectively registered. Initial surgery was suggested only if possible without mutilation. Patients with initial complete (IRS-group I/R0) or microscopic incomplete (group II/R1) resection had no further therapy. Patients with initial inoperable tumour (group III/R2) received first-line vincristine-actinomycin-D chemotherapy (VA). Delayed conservative surgery was planned after tumour reduction. Aggressive local therapy (mutilating surgery or external radiotherapy) was discouraged. RESULTS: A total of 50 infants (median age 1.4 months), were included in the study. ETV6-NTRK3 transcript was present in 87.2% of patients where investigation was performed. According to initial surgery, 11 patients were classified as group I, 8 as group II and 31 as group III. VA chemotherapy was first delivered to 25 children with IRS-III/R2 and one with IRS-II/R1 disease. Response rate to VA was 68.0%. Mutilating surgery was only performed in three cases. After a median follow-up of 4.7 years (range 1.9-9.0), 3-year event-free survival and overall survival were respectively 84.0% (95% confidence interval [CI] 70.5-91.7) and 94.0% (95% CI 82.5-98.0). CONCLUSIONS: Conservative therapy is possible in IFS as only three children required mutilating surgery, and alkylating or anthracycline based chemotherapy was avoided in 71.0% of patients needing chemotherapy. VA regimen should be first line therapy in order to reduce long term effects.

The Role of Computed Tomography Scanning of the Thorax in the Initial Assessment of Gestational Trophoblastic Neoplasia.

OBJECTIVE: The aim of this study was to determine whether lesions found on computed tomography (CT) imaging of the thorax would affect FIGO (International Federation of Gynecology and Obstetrics) 2000 risk score and/or alter clinical management. METHODS: The Sheffield Trophoblastic Disease database was searched for all new patients registered for staging/scoring investigations between January 1, 2006, and June 30, 2010. The FIGO 2000 score was noted and then recalculated using information from CT scan reports. Where a change of risk score would have affected a patient's management, the case notes were further reviewed. RESULTS: 191 patients had undergone both modalities of imaging. Using standard FIGO scoring, 169 and 22 patients were noted to be at low and high risk, respectively. Using information from CT imaging, only a further 20 patients would have been reclassified as high risk. Fifteen of these "new" high-risk patients required salvage treatment with intravenous chemotherapy; all were cured. CONCLUSIONS: With no potential advantage in terms of patient outcome and significantly increased radiation dose, there is little justification for routine CT imaging of the thorax in the initial assessment of new patients with gestational trophoblastic neoplasia.

Inpatient versus outpatient vincristine, dactinomycin, and cyclophosphamide for pediatric cancers: Quality and cost implications.

BACKGROUND: Approximately 18% of the United States' gross domestic product is attributed to healthcare expenditures. Several studies have illustrated that shifting healthcare from the inpatient to the outpatient setting is more cost effective, in addition to improving patient satisfaction. Vincristine, dactinomycin, and cyclophosphamide (VAC) are used together to treat children with solid tumors. Our traditional treatment approach included a two day inpatient admission. The purpose of this project was to establish a process for the administration of VAC in the outpatient setting to improve satisfaction, and reduce costs. PROCEDURE: We aimed to benchmark practice standards with other institutions, revised our treatment approach to permit outpatient administration, and implemented the new protocol in a stepwise manner. We collected caregiver satisfaction metrics through the use of surveys. Costs of encounters were obtained from administrative data. Total costs and costs by service type were compared using descriptive and mean comparisons. RESULTS: Seven patients received a total of 31 cycles of VAC in the outpatient setting. The time to achieve an appropriate pre-chemotherapy specific gravity was reduced by a median of 120 min. In addition, time spent in the hospital setting was reduced by a mean of 27.2 hr. Adverse effects were minimal and all caregivers reported greater satisfaction with the outpatient regimen. Outpatient administration of VAC was $3,300 less on average compared to the inpatient administration. CONCLUSION: Outpatient VAC provides a safe alternative for administration that reduces healthcare costs, reduces healthcare utilization, and improves patient satisfaction.

Brain metastases in gestational trophoblast neoplasia: an update on incidence, management and outcome.

OBJECTIVE: To update the demographic data, treatment details and outcomes for GTN patients with brain metastases managed with the modern treatment protocols at the UK centre for gestational trophoblast neoplasia at Charing Cross Hospital in London. METHODS: The hospital database and pharmacy records were reviewed to identify GTN patients treated with brain metastases. Data was assembled on the specific GTN diagnosis, staging, prognostic scores, chemotherapy regimens, additional interventions and outcomes. RESULTS: During the 22 year study period, 27 GTN patients with brain metastases were treated. One case clearly resulted from a prior molar pregnancy, 3 were of uncertain aetiology and 23 cases had no prior molar pregnancy. The standard chemotherapy regimens were EMA-CO or EMA-EP given with an enhanced CNS methotrexate dose combined with intrathecal methotrexate. Five patients required emergency neurosurgery and routine radiotherapy was not employed. Twenty three (85%) patients are long term survivors and four patients died. Of the patients who died, all four had chemotherapy refractive disease and two had extended intervals of 18 and 30 years from their antecedent pregnancy. CONCLUSION: The incidence of brain metastases in postmolar pregnancy GTN is extremely low. Patients with non-molar choriocarcinoma have an approximate 20% risk of CNS disease and should have routine CNS imaging. Treatment with CNS doses of EMA-CO or EMA-EP appears curative for most patients.

Clinical epidemiology and management of gestational trophoblastic neoplasia in Hungary in the past 34 years.

OBJECTIVE: To review our clinical experience in the treatment of patients with gestational trophoblastic neoplasia (GTN) over the past 34 years in our national trophoblastic disease center. STUDY DESIGN: Between January 1, 1977, and December 31, 2010, 331 patients with low-risk GTN and 174 patients with high-risk GTN (altogether 505) were treated. The patients were directed to the national trophoblastic disease center from all parts of Hungary. The patients were between 14 and 54 years of age, with an average age of 28.7 years. Primary chemotherapy was selected based upon the patient's stage and prognostic score of GTN. RESULTS: Among 237 low-risk patients, 228 (96.2%) achieved remission as a result of primary methotrexate (MTX) therapy. Out of 94 low-risk patients 90 (95.7%) achieved remission as a result of primary actinomycin-D (Act-D) therapy. MTX, Act-D and cyclophosphamide (MAC) as a primary therapy was used in 118 high-risk cases, and 110 (93.2%) patients achieved complete remission. A total of 32 high-risk patients were treated with the etoposide, high-dose MTX/folinic acid, Act-D, cyclophosphamide and vincristine (EMA-CO) regimen, and of 26 primary therapies complete remission was achieved in 21 (80.8%) cases. Primary cisplatin, etoposide and bleomycin (CEB) therapy was successful in 16 of 17 high-risk cases (94.1%). Metastases were found in 47.3% (239/505) of the patients. Hysterectomy was performed in 68 of 505 (13.5%) cases. Chemotherapy, surgical intervention or other supplementary treatments resulted in 100% remission in cases of nonmetastatic and metastatic low-risk disease. Comparison of mean prognostic scores resulted in significant differences between CEB and MAC, CEB and EMA-CO, and MAC and EMA-CO. CONCLUSION: Our data indicate that MTX/folinic acid or Act-D should be the primary treatment in patients with nonmetastatic or metastatic low-risk GTN. Patients with high-risk metastatic GTN should be treated primarily with combination chemotherapy. Our data support the effectiveness of MAC, EMA-CO and CEB regimens. Results also show that patient care under the direction of experienced clinicians serves to optimize the opportunity for cure and minimize morbidity.

A cost analysis of first-line chemotherapy for low-risk gestational trophoblastic neoplasia.

OBJECTIVE: To determine the optimal approach to first-line treatment for low-risk gestational trophoblastic neoplasia (GTN) using a cost analysis of 3 commonly used regimens. STUDY DESIGN: A decision tree of the 3 most commonly used first-line low-risk GTN treatment strategies was created, accounting for toxicities, response rates and need for second- or third-line therapy. These strategies included 8-day methotrexate (MTX)/folinic acid, weekly MTX, and pulsed actinomycin-D (act-D). Response rates, average number of cycles needed for remission, and toxicities were determined by review of the literature. Costs of each strategy were examined from a societal perspective, including the direct total treatment costs as well as the indirect lost labor production costs from work absences. Sensitivity analysis on these costs was performed using both deterministic and probabilistic cost-minimization models with the aid of decision tree software (TreeAge Pro 2011, TreeAge Inc., Williamstown, Massachusetts). RESULTS: We found that 8-day MTX/folinic acid is the least expensive to society, followed by pulsed act-D ($4,867 vs. $6,111 average societal cost per cure, respectively), with act-D becoming more favorable only with act-D per-cycle cost <$231, or response rate to first-line therapy > 99%. Weekly MTX is the most expensive first-line treatment strategy to society ($9,089 average cost per cure), despite being least expensive to administer per cycle, based on lower first-line response rate. Absolute societal cost of each strategy is driven by the probability of needing expensive third-line multiagent chemotherapy, however relative cost differences are robust to sensitivity analysis over the reported range of cycle number and response rate for all therapies. CONCLUSION: Based on similar efficacy and lower societal cost, we recommend 8-day MTX/folinic acid for first-line treatment of low-risk GTN.

Decision analysis to compare treatment strategies for Stage I/favorable histology Wilms tumor.

BACKGROUND: Decision analysis was used to clarify differences in survival and complication rates comparing surgery alone versus surgery plus chemotherapy for Stage I, favorable histology Wilms tumor patients. PROCEDURE: A state transition model was used to simulate treatment with nephrectomy-only, nephrectomy with adjuvant vincristine (VCR) or with vincristine plus dactinomcyin (NWTS Regimen EE4A). Rates of relapse and complications of therapy were obtained from the literature. In sensitivity analysis, the model was probed for the value(s) at which the treatment of choice changes. RESULTS: The overall survival (OS) is essentially the same for patients treated with any of the three strategies (OS(Nephrectomy) = 98.8%; OS(EE4A) = 98.8%; OS(VCR) = 98.6%). Rates of serious long-term complications in the surviving population are also similar across treatment strategies (nephrectomy = 1.4%; VCR = 1.2%; EE4A = 0.3%). Both the progression and salvage rates after nephrectomy-only would have to be much worse than expected for nephrectomy-only to be an unacceptable strategy. CONCLUSIONS: The differences in overall survival and rates of long-term complications between the three different initial strategies were negligible in the model. Based on this analysis, it was decided by the Children's Oncology Group that it was acceptable to continue to include nephrectomy without adjuvant chemotherapy as an experimental arm of the low risk Wilms tumor protocol with stringent eligibility criteria and close follow-up. Decision analysis can have a role in clinical trial design by making the tradeoffs between strategies more explicit. The robustness of these conclusions can be tested by widely varying the underlying assumptions.

Results of the EICESS-92 Study: two randomized trials of Ewing's sarcoma treatment--cyclophosphamide compared with ifosfamide in standard-risk patients and assessment of benefit of etoposide added to standard treatment in high-risk patients.

PURPOSE: The European Intergroup Cooperative Ewing's Sarcoma Study investigated whether cyclophosphamide has a similar efficacy as ifosfamide in standard-risk (SR) patients and whether the addition of etoposide improves survival in high-risk (HR) patients. PATIENTS AND METHODS: SR patients (localized tumors, volume <100 mL) were randomly assigned to receive four courses of vincristine, dactinomycin, ifosfamide, and doxorubicin (VAIA) induction therapy followed by 10 courses of either VAIA or vincristine, dactinomycin, cyclophosphamide, and doxorubicin (VACA; cyclophosphamide replacing ifosfamide). HR patients (volume >or=100 mL or metastases) were randomly assigned to receive 14 courses of either VAIA or VAIA plus etoposide (EVAIA). Outcome measures were event-free survival (EFS; defined as the time to first recurrence, progression, second malignancy, or death) and overall survival (OS). RESULTS: A total of 647 patients were randomly assigned: 79 SR patients were assigned to VAIA, 76 SR patients were assigned to VACA, 240 HR were assigned to VAIA, and 252 HR patients were assigned to EVAIA. The median follow-up was 8.5 years. In the SR group, the hazard ratios (VACA v VAIA) for EFS and OS were 0.91 (95% CI, 0.55 to 1.53) and 1.08 (95% CI, 0.58 to 2.03), respectively. There was a higher incidence of hematologic toxicities in the VACA arm. In the HR group, the EFS and OS hazard ratios (EVAIA v VAIA) indicated a 17% reduction in the risk of an event (95% CI, -35% to 5%; P = .12) and 15% reduction in dying (95% CI, -34% to 10%), respectively. The effect seemed greater among patients without metastases (hazard ratio = 0.79; P = .16) than among those with metastases (hazard ratio = 0.96; P = .84). CONCLUSION: Cyclophosphamide seemed to have a similar effect on EFS and OS as ifosfamide in SR patients but was associated with increased toxicity. In HR patients, the addition of etoposide seemed to be beneficial.

[Assessment of staging and prognostic scoring system for malignant trophoblastic neoplasia].

OBJECTIVE: To assess malignant trophoblastic neoplasia with the standards of the clinical stage and prognostic factor scoring system. METHODS: Through assessing the high-risk factors except clinical stages for 223 patients before treatment according to International Federation of Gynecology and Obstetrics (FIGO) scoring system published in 2000, appropriate treatments were selected for the different patients. RESULTS: Forty-three of 78 cases of choriocarcinomas were with high-risk factors, the other 35 cases were with low-risk factors; 7 of 145 cases of invasive moles were with high-risk factors and the others were with low-risk factors. The primary chemotherapy principle was that one agent was used for those patients with low-risk factors and two or multiple-agents were used for those patients with high-risk factors. Among all patients, the one-year, three-year and five-year survival rates were 98.6%, 98.1% and 97.1% respectively. No patient died of drug toxicity or complication. CONCLUSION: Selection of treatment approaches according to the prognostic assessment of malignant trophoblastic neoplasia could lead to promising survival rate with no uncurable complication and toxic effects.

Assessment of systemic toxicity in children receiving chemotherapy with cyclosporine for sarcoma.

BACKGROUND: Overexpression of P-glycoprotein in malignant tumors has been associated with poor responses to chemotherapy. It appears biologically plausible that addition of the P-glycoprotein inhibitor cyclosporine (CsA) to standard chemotherapy may improve the outcome. The protective functions of P-glycoprotein in healthy tissues, however, have not been fully elucidated. Addition of CsA may lead to increased systemic chemotherapy toxicity, so we compared the rate and severity of chemotherapy-associated systemic toxicity in the presence and absence of CsA. PROCEDURE: Standard chemotherapy consisted of etoposide/ifosfamide (VP16/IFOS) cycles, alternating with vincristine/dactinomycin/cyclophosphamide (VAC) cycles. CsA was given at a median dose of 20 mg/kg with unaltered doses of the antineoplastic drugs. The analysis of toxicity was performed by comparing clinically significant toxicity events recorded during and after chemotherapy cycles with and without CsA. RESULTS: Toxicity-related hospital admissions occurred after 93% of VAC cycles with CsA compared to 40% of the cycles without CsA (P < 0. 0001); 29% of VP16/IFOS cycles with CsA led to admissions vs. 12% with non-CsA cycles (P = 0.04). Infections or fever and neutropenia were the main reasons for these admissions. Thirty-seven percent of the VAC cycles with CsA were complicated by culture-proved sepsis, which did not occur in cycles without CsA (P < 0.0001). Requirements for blood and platelet transfusions were greatly increased after VAC cycles with CsA compared to VAC cycles without CsA. CONCLUSIONS: The chemosensitizer CsA increases the systemic toxicity of VAC chemotherapy in patients with sarcomas. Future trials of chemotherapy with chemosensitizers will have to take into account a potential increase in systemic toxicity. Careful monitoring of chemotherapy-related toxicity becomes mandatory in such studies.

Clinical assessment of EMA/CO induced DNA damage in peripheral blood lymphocytes of high-risk gestational trophoblastic tumor patients.

From 1989 to 1994, Etoposide, Methotrexate, Actinomycin-D, Cyclophosphamide, Vincristine, Folic acid (EMA/CO) regimen was administered to seven patients with high-risk gestational tumours according to the Bagshawe 1976 criteria. Peripheral blood lymphocytes were obtained from two of these seven high-risk gestational trophoblastic patients receiving the EMA/CO regimen, and damage levels of DNA during chemotherapy were assessed using SCGE (single cell gel electrophoresis) assay. Additionally, the efficacy, toxicity and clinical results of EMA/CO regimen were evaluated in patients with high-risk gestational trophoblastic tumours. Fever (71.4%), leukopenia (57%), increase in transaminase concentrations (57%), trombocytopenia (57%), and anemia (57%) were among the most frequent side-effects of the EMA/CO regimen. All these toxic effects were reversible and there was no need to stop the therapy. EMA/CO is highly effective in patients with high-risk gestational trophoblastic disease and its toxicity is predictable and reversible. Because of chemotherapy, DNA damage that is shown in peripheral blood lymphocytes, increases at the 8th day of the EMA/CO regimen. When DNA damage is higher in patients, the course of chemotherapy per each patient is shortened. When DNA damage is higher in the patients, the multisystem effects due to toxicity are more significant. The SCGE assay has many possibilities in such research and has proved to be a relatively simple, quick and sensitive technique.

Effect of duration of treatment on treatment outcome and cost of treatment for Wilms' tumor: a report from the National Wilms' Tumor Study Group.

PURPOSE: National Wilms' Tumor Study (NWTS)-4 was designed to evaluate the efficacy, toxicity, and cost of the administration of different regimens for the treatment of Wilms' tumor (WT). PATIENTS AND METHODS: Between August 6, 1986 and September 1, 1994, 905 previously untreated children aged younger than 16 years with stage II favorable histology (FH) WT (low-risk [LR]), stages III to IV FH WT, or stages I to IV clear-cell sarcoma of the kidney (high-risk[HR]) were randomized after the completion of 6 months of chemotherapy to discontinue (short) or continue for 9 additional months (long) treatment with chemotherapy regimens that included vincristine and either divided-dose (standard [STD]) courses (5 days) or single-dose (pulse-intensive [PI]) treatment with dactinomycin. HR patients also received either divided-dose (STD) courses (3 days) or single-dose (PI) treatment with doxorubicin. RESULTS: The 4-year relapse-free survival (RFS) rates after the second randomization for LR patients were 83.7% for the 190 patients treated with short and 88.2% for the 187 patients treated with long chemotherapy (P = .11). The 4-year RFS rates after the second randomization for HR FH patients were 89.7% for the 256 patients treated with short and 88.8% for the 246 patients treated with long chemotherapy (P = .87). The charge for treatment with the short PI treatment regimens for all children with stages I through IV FH WT was approximately one half of that with the long STD treatment regimens. CONCLUSION: The short administration schedule for the treatment of children with WT is no less effective than the long administration schedule and can be administered at a substantially lower total treatment cost.

The assessment of value of transvaginal ultrasound for monitoring of gestational trophoblastic disease treatment.

Thirtysix patients with persistent gestational trophoblastic disease were analysed in The Clinic of Cancer of Female Reproductive System. Using transvaginal USG, the volume of pathological foci within myometrium, diametre of theca lutein ovarian cysts and uterus length before, during and after the treatment were registred. In order to check the effectiveness of USG examination in the monitoring of GTD treatment particular USG factors were compared with hCG level. On 28 patients (77.7%) in USG examination pathological changes in uterus and ovaries were seen. The relation between hCG level and tumor volume, uterus length and theca lutein ovarian cysts was stated. That proves the usefulness of transvaginal USG examination in the monitoring of treatment of patients with persistent gestational trophoblastic disease.

Relationship between dose schedule and charges for treatment on National Wilms' Tumor Study-4. A report from the National Wilms' Tumor Study Group.

National Wilms' Tumor Study-4 was designed to evaluate the efficacy, toxicity, and cost of administration of different regimens for the treatment of Wilms' tumor. The charges for treatment with dactinomycin and doxorubicin administered by two different schedules were calculated using current charges in Buffalo, N.Y. An annual savings of approximately $779,259 could be achieved by the use of the short, pulse-intensive (i.e., single-dose) treatment regimens for all children with Wilms' tumor of stages I-IV/favorable histology. The pulse-intensive administration schedule for the treatment of children with Wilms' tumor permits administration of chemotherapy at a substantially lower total treatment cost.

Occurrence, clinical behaviour and management of Kaposi's sarcoma in Zambia.

The incidence of HIV related KS has increased 50-fold since it was first recognized in Zambia in 1983. The mean age at diagnosis is 35 years for men and 28 years for women, with a sex ratio of M:F = 5:1. The most common symptoms and signs are weight loss, symmetrical lymphadenopathy, oral plaques, skin plaques in a central distribution, oedema and cough with dyspnoea. Biopsy is needed to confirm the diagnosis if disease is confined to lymph nodes. Objective regression occurs in 80% of patients receiving adequate doses of actinomycin D and vincristine (median survival time greater than 3 years for stage I or II disease and 7.5 months for stage III); epirubicin with vincristine was more effective in a phase II trial. Both treatments give good relief of symptoms, allowing patients to return to work. Clinical, histological and biological features of HIV related KS do not support conclusively its classification as a "malignant tumour". Heterosexual and perinatal transmission of HIV in Africa ensures that KS affects families, not just individuals.

Weekly intramuscular methotrexate for nonmetastatic gestational trophoblastic disease.

Patients with nonmetastatic gestational trophoblastic disease were entered into this Gynecologic Oncology Group study to determine the efficacy, toxicity, and cost-effectiveness of weekly intramuscular (IM) methotrexate. Treatment was initiated with 30 mg/m2 of weekly IM methotrexate. If no major toxicity was encountered, the weekly dose was escalated 5 mg/m2 at three-week intervals until a maximum dose of 50 mg/m2 each week was achieved. Complete response was defined as three normal beta-hCG values measured on consecutive weeks. Fifty-one of 63 evaluable patients (81%) had a complete response to weekly IM methotrexate. Duration of therapy ranged from three to 19 weeks, with a median of seven. No major toxicity occurred. Thirteen patients experienced leukopenia at a median of 3300/microL, with a range of 2300-3900. Three patients had platelet nadirs of 66,000, 127,000, and 135,000/microL. Eleven patients with weekly IM methotrexate failure had a complete response after one to eight courses of dactinomycin administered 0.5 mg/m2 intravenously daily for five days; one refused therapy after three courses. Weekly IM methotrexate for nonmetastatic gestational trophoblastic disease is efficacious, minimally toxic, and cost-effective.

Pulse actinomycin D scheduling in nonmetastatic gestational trophoblastic neoplasia: cost-effective chemotherapy.

The currently accepted method of treatment of patients with nonmetastatic gestational trophoblastic neoplasia (NMGTN) is single-agent chemotherapy. While methotrexate and actinomycin D have shown superiority over other cytotoxic agents, doses of drug and length of treatment are subject to controversy. Recently, the demonstration of the long half-life of actinomycin D in both animal models and humans has necessitated a reevaluation of the method of administration of this drug for NMGTN. Following the demonstration of minimal severe toxicity of pulse actinomyin-D scheduling by E. S. Petrilli and C. P. Morrow (Actinomycin D toxicity in the treatment of trophoblastic disease, Gynecol. Oncol. 9, 18-22 (1980), 12 consecutive patients with nonmetastatic gestational trophoblastic neoplasia were treated. The remission rates, toxicity, and cost effectiveness of pulse actinomycin-D scheduling in these 12 patients are reported.