Vincristine, Dactinomycin, Cyclophosphamide Research Articles

Presentación atípica de masas en mama de 2 meses de evolución, reporte de caso clínico

Primary breast rhabdomyosarcoma is a pathology of low incidence in our environment and worldwide, the most frequent subtype is alveolar rhabdomyosarcoma; it occurs more frequently in children and adolescents; its etiology is unknown, but it is associated with previous treatments with radiotherapy, chemotherapy, genetic syndromes, among others. The standard panel for diagnosis is immunohistochemistry using markers such as desmin, vimentin, myogenin. Treatment requires a multidisciplinary approach comprising surgical treatment, first-line chemotherapy scheme VAC (vincristine, dactinomycin, cyclophosphamide), and radiotherapy. The 5-year survival median is 44%. The case of a 24-year-old female patient is presented, who presents with lymphadenopathy in the neck, mass in the infraorbital region, lymphadenopathy at the supraclavicular level and in the breasts, the picture is accompanied by thermal rise, ecchymosis in the extremities together with left subconjunctival hemorrhage ; They perform complementary tests and diagnose high-risk non-Hodgkin's lymphoma, stage IV with infiltration to the bone marrow with B symptoms plus Burkitt mass plus extranodal mediastinal mass, for which treatment with chemotherapy with RCHOP scheme (rituximab, cyclophosphamide, vincristine, doxorubicin, prednisone); She received 8 cycles with clinical improvement, followed by revision of lamellae, the first biopsy of the right breast, giving the diagnosis of alveolar rhabdomyosarcoma.

Late dental effects of chemotherapy and radiotherapy in childhood cancer survivor: case report

Chemotherapy drugs and radiotherapy in the head and neck region are considered possible to interfere with odontogenesis. Patients may present alterations such as tooth agenesis, shortening or root malformation, enamel hypoplasia and microdontia. Such effects do not occur in adults, as they already have the dental structures formed. The objective of this study is to describe, through a case report, the dental alterations and implications for the clinical practice of a patient who received chemotherapy and radiotherapy in childhood. A 12- year-old female patient was diagnosed with embryonal rhabdomyosarcoma in the right parotid gland region at 5 years of age. Antineoplastic treatment consisted of IRS IV chemotherapy protocol: ifosfamide (IFO) - doxorubicin (DOXO) - etoposide (VP16) followed by vincristine - dactinomycin - cyclophosphamide (VAC) / vincristine - ifosfamide - etoposide (VIE) alternated, in addition to conventional radiotherapy, with a total dose of 45 Gy. The patient developed important dental alterations, such as root malformation in most teeth, microdontia and enamel hypoplasia, being essential the role of the dentist. Currently, after 6 years of anticancer treatment, she has regular dental follow-up.

Alveolar rhabdomyosarcoma with regional nodal involvement: Results of a combined analysis from two cooperative groups

Treatment of children and adolescents with alveolar rhabdomyosarcoma (ARMS) and regional nodal involvement (N1) have been approached differently by North American and European cooperative groups. In order to define a better therapeutic strategy, we analyzed two studies conducted between 2005 and 2016 by the European paediatric Soft tissue sarcoma Study Group (EpSSG) and Children's Oncology Group (COG). We retrospectively identified patients with ARMS N1 enrolled in either EpSSG RMS2005 or in COG ARST0531. Chemotherapy in RMS2005 comprised ifosfamide + vincristine + dactinomycin + doxorubicin (IVADo), IVA and maintenance (vinorelbine, cyclophosphamide); in ARST0531, it consisted of either vincristine+dactinomycin+cyclophosphamide (VAC) or VAC alternating with vincristine+irinotecan (VI). Local treatment was similar in both protocols. The analysis of the clinical characteristics of 239 patients showed some differences between study groups: in RMS2005, advanced Intergroup Rhabdomyosarcoma Study Group (IRS) and large tumors predominated. There were no differences in outcomes between the two groups: 5-year event-free survival (EFS), 49% (95% confidence interval [CI]: 39-59) and 44% (95% CI: 30-58), and overall survival (OS), 51% (95% CI: 41-61) and 53.6% (95% CI: 40-68) in RMS2005 and ARST0531, respectively. In RMS2005, EFS of patients with FOXO1-positive tumors was significantly inferior to those with FOXO1-negative (49.3% vs 73%, P=.034). In contrast, in ARST0531, EFS of patients with FOXO1-positive tumors was 45% compared with 43.8% for those with FOXO1-negative. The outcome of patients with ARMS N1 was similar in both protocols. However, patients with FOXO1 fusion-negative tumors enrolled in RMS2005 showed a significantly better outcome, suggesting that different strategies of chemotherapy may have an impact in the outcome of this subgroup of patients.

The VAC regimen for adult rhabdomyosarcoma: Differences between adolescent/young adult and older patients.

Compared to pediatric patients, adult rhabdomyosarcoma (RMS) patients have poor prognoses, but the differences in prognoses and treatment sensitivity between adolescent/young adult (AYA) patient and older RMS patients have not been established. To evaluate and compare the efficacy and safety of the vincristine/dactinomycin/cyclophosphamide (VAC) regimen, that is, the standard combination chemotherapy regimen for pediatric RMS, in AYA and older patients. We retrospectively reviewed the clinical records of adolescent and adult RMS patients treated at our institution and patients treated with the VAC were enrolled in the analyses. The differences in the efficacy and safety of VAC between the AYA patients (15-39 years old) and older patients (≥40 years old) were compared. Total of 23 patients were enrolled (14 AYA patients and nine older patients) were enrolled. With the median follow-up of 89.4weeks (range 17.7-263.1weeks), the median progression-free survival (PFS) and overall survival (OS) of the VAC regimen were 61.4weeks (95% CI, 32.6-90.3) and 104.0weeks (95% CI, 43.8-164.2), respectively, with no significant differences in the PFS or OS between the AYA and older patients. There were no differences in the response rate of the VAC between AYA (64.3%) and older (66.7%), either. Safety profiles were similar between the AYA and older groups, but exposure to antitumor drugs of the VAC tended to be lower in the older group; median number of total cycle of the VAC was 13 in AYA and 10 in older, cumulative cyclophosphamide dose was 16.8g/m2 in AYA and 12.8g/m2 in older, and number of vincristine skips was six in AYA and 12 in older, respectively. There were no significant differences in responses to the VAC among AYA and older patients with RMS. With the appropriate dose modification, the VAC regimen could be a feasible treatment option for RMS patients>40 years old.

Chemotherapy for gestational trophoblastic neoplasia patients with a FIGO score of 12 or greater: A multistudy analysis

ObjectiveTo enable a comparison of reported chemotherapy regimens in gestational trophoblastic neoplasia (GTN) patients with a International Federation of Gynecology and Obstetrics (FIGO) score ≥12. Study designStudies reporting cases of GTN with a FIGO score ≥12 were collected and screened for eligibility. A total of 17 studies encompassing 256 patients were included in final analysis. ResultsIn the first-line setting, etoposide-methotrexate-dactinomycin alternating with cyclophosphamide-vincristine (EMA/CO), etoposide-platinum alternating with EMA (EP/EMA), and floxuridine-dactinomycin-etoposide-vincristine (FAEV) were the three most commonly used regimens. The complete response (CR) rate was 55.2% for EMA/CO, 60.0% for EP/EMA, and 63.1% for FAEV. There was no significant difference in CR rate among EMA/CO, EP/EMA and FAEV in the first-line setting. While limited by low number, the CR rate was 66.67% for methotrexate-bleomycin -etoposide (MBE), and 25% for vincristine-dactinomycin-cyclophosphamide (VAC). Of the patients who failed initial therapy, EMA/CO, EP/EMA, and paclitaxel- cisplatin alternating with paclitaxel-etoposide (TP/TE) were the three most commonly used salvage regimens. The CR rate was 39.7% for EMA/CO, 35.0% for EP/EMA, and 11.8% for TP/TE. While limited by low number, MBE was used in 5 patients and yielded a 80% CR rate. Of the fatal cases, 21 (61.8%) patients had brain metastases, and 41.2% (14/34) of the deaths were early deaths. ConclusionEMA/CO, EP/EMA, and FAEV yielded comparable CR rates in GTN patients with a FIGO score ≥12 in the first-line setting.

Intracranial atypical teratoid rhabdoid tumor: current management and a single institute experience of 15 patients from north India.

We intended to assess the clinicopathological features and treatment outcome in patients of intracranial atypical teratoid rhabdoid tumor (AT/RT), a rare malignant tumor of the brain. Medical records were reviewed and clinical data collected on AT/RT in a 6-year period (2006-2012). Overall survival was analyzed by Kaplan-Meier method. Univariate analysis of factors predictive of overall survival was done by log-rank test. Fifteen patients met the study criterion (male:female = 4:1). Median age at presentation was 5 years (range, 0.8-8 years). Presenting complaints included vomiting (73.33 %), headache (46.67 %), orbital symptoms (33.33 %), motor impairment (26.67 %), gait abnormality (20 %), and seizure (20 %). Median duration of symptoms was noted to be 2 months (range, 0.5-6 months). On contrast-enhanced MRI of brain, tumor location was supratentorial in 60 % patients and infratentorial in 40 % of patients. Cystic component and hydrocephalus were noted in 73.33 % patients each, whereas contrast enhancement and calcification were discerned in 53.33 and 40 % of the patients, respectively. All patients underwent tumor resection-gross total (26.67 %), near-total (13.33 %) and subtotal (60 %). Histopathology was confirmative of AT/RT with MIB-1 labeling index varying from 11 to 85 % (median 45 %). There was a lack of immunostaining for INI-1 protein, suggesting INI-1gene mutation or deletion. Adjuvant radiation (36 Gray/20 fractions/4 weeks to entire neuraxis followed by local boost 20 Gray/10 fractions/2 weeks) was started in six patients (40 %) and completed in five patients. Young age at presentation and poor performance status precluded the use of radiation in the remainder. Systemic chemotherapy was administered in ten (66.67 %) patients. Median number of cycles given was three (range, 1-12) with ICE (ifosfamide, carboplatin, etoposide) and VAC (vincristine, dactinomycin, cyclophosphamide) being the common regimens (26.67 and 20 %, respectively). After a median follow-up of 8.33 months (mean, 12.27 months), median overall survival was noted to be 10 months. At last follow-up, two patients are in complete response, one patient is on treatment, three patients are alive with evidence of disease, and nine patients expired due to disease progression. The 1- and 2-year actuarial rate of overall survival was noted to be 48.1 and 24.1 %, respectively. On univariate analysis, extent of surgery (p = 0.0149), use of craniospinal radiation (p = 0.0087), and MIB1 labeling index (p = 0.0034) were significant predictors of overall survival while age (≥5 years versus <5 years) was of borderline significance (p = 0.08). Median survival of 10 months reflects the aggressive biology of this rare neoplasm. Maximal safe resection followed by craniospinal irradiation and systemic chemotherapy with ICE or VAC regimen is a reasonable treatment strategy in this uncommon malignancy.

Vincristine, dactinomycin, cyclophosphamide (VAC) versus VAC/V plus irinotecan (VI) for intermediate-risk rhabdomyosarcoma (IRRMS): A report from the Children’s Oncology Group Soft Tissue Sarcoma Committee.

10004 Background: The long-term event free survival (EFS) for IRRMS is 65%. Since VI had significant activity in metastatic and recurrent RMS, we tested whether adding VI to VAC would improve EFS for IRRMS. Methods: Patients (pts) with alveolar (A)RMS or incompletely resected (Group III) embryonal (E)RMS arising in an unfavorable primary site (Stage 2/3), both without distant metastases, < 50 years, and adequate organ function were eligible to be randomized to 42 weeks of VAC (V=1.5 mg/m2, A=0.045 mg/kg, C=1.2 g/m2 every 3 weeks) vs VAC/VI (I=50 mg/m2/day x 5 days) intravenously; doses were adjusted for children < 3 years; radiation therapy (36-50.4 Gy) was started at week 4, with individualized local control for children < 2 years allowed. The primary study endpoint was EFS. The study was designed with 80% power (5% 1-sided alpha level) to detect an increase in 5 yr EFS from 65% to 76%, a relative risk of 0.64. Results: 481 pts were entered between 12/2006-12/2012, with 461 confirmed eligible. Clinical f...

Paratesticular Alveolar Rhabdomyosarcoma with Multiple Lymph Nodes Metastasis Successfully Treated with Chemotherapy

Rhabdomyosarcomas are soft tissue sarcomas; while extremely rare in adults, they are one of the most common neoplasms in children and adolescents. Histologically, they can be classified into embryonal (ERMS), alveolar (ARMS), pleomorphic, and undifferentiated types. The ARMS type is very rare, and is associated with a poor prognosis. Common primary sites of ARMS are the trunk and extremities. We report on a case of paraaortic, supraclavicular, and axillary lymph node metastasis from paratesticular ARMS treated with VAC (vincristine, dactinomycin, cyclophosphamide)/ IE(ifosfamide, etoposide) chemotherapy in a young adult. Administration of six cycles of chemotherapy with VAC/IE resulted in complete remission. The patient has maintained complete remission over the past 27 months.

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. Med. Pediatr. Oncol. 34:242–249, 2000. © 2000 Wiley-Liss, Inc.

Ewing's sarcoma of soft tissues in childhood: a report from the Intergroup Rhabdomyosarcoma Study, 1972 to 1991.

One hundred thirty of 2,792 patients (5%) registered on three Intergroup Rhabdomyosarcoma Study clinical trials (IRS-I, -II, and -III) from 1972 to 1991 had an extraosseous Ewing's sarcoma (EOE). We report here the results of multimodality therapy for this tumor. The 130 patients were less than 21 years of age; 70 (54%) were males. Primary tumor sites were on the trunk in 41 patients, an extremity in 34, the head/neck in 23, the retroperitoneum/pelvis in 21, and other sites in 11. One hundred fourteen patients had no metastases at diagnosis. In 21 patients, the tumor was completely resected; in 30, the localized or regional tumor was grossly resected, and in 63 patients, grossly visible sarcoma was left behind. Sixteen patients (12%) had distant metastases at diagnosis. All patients were given multiagent chemotherapy and most received irradiation (XRT); none were treated with bone marrow transplantation. One hundred seven patients (82%) achieved a complete response. At 10 years, 62%, 61%, and 77% of the patients were alive after treatment on IRS-I, IRS-II, or IRS-III therapeutic protocols, respectively, similar to figures obtained in all IRS patients. At last follow-up evaluation, 42 patients had died of progressive tumor and one of infection. Survival at 10 years was most likely for patients with tumor that arose in the head and neck, extremities, and trunk, and for those who underwent grossly complete tumor removal before initiation of chemotherapy. For patients with localized, gross residual tumor, adding doxorubicin (DOX) to the combination of vincristine, dactinomycin, cyclophosphamide (VAC), and XRT did not significantly improve survival in 39 patients (62% alive at 10 years) compared with that of 24 patients treated with VAC and XRT without DOX (65% alive at 10 years, P = .93). This series indicated that EOE in children is similar to rhabdomyosarcoma (RMS) in its response to multimodal treatment. No benefit was apparent from the addition of DOX to VAC chemotherapy in patients with gross residual EOE.

Bone marrow metastases at diagnosis in children and adolescents with rhabdomyosarcoma. A report from the intergroup rhabdomyosarcoma study.

Thirty children and adolescents with rhabdomyosarcoma (RMS) entered on IRS-1 in a 5-year period had bone marrow metastases (BMM) at diagnosis. BMM at diagnosis occurred in 30/103 patients (29%) with Clinical Group IV RMS. On the average, patients with BMM were older with more extremity primaries than other IRS-1 patients. Alveolar histology was present in 15/30 patients (50%) with BMM, compared to 19% on IRS-1. Eleven patients received vincristine, dactinomycin, cyclophosphamide (VAC), while 19 patients received VAC with Adriamycin (ADR). The overall complete response (CR) rate was 60%. The median disease-free survival times by treatment were 17 weeks with VAC and 32 weeks for VAC + ADR (P greater than 0.10). Relapse from CR in Clinical Group IV patients with BMM occurred in 16/18 patients (89%) and was significantly higher than in 17/29 Clinical Group IV patients (59%) without BMM (P less than 0.035). BMM at diagnosis in children and adolescents with RMS is frequently associated with alveolar histology and is a poor prognostic sign.