Courses Of VP-16 Research Articles

New challenges in retinoblastoma treatment

PurposeRetinoblastoma treatment has changed during the past ten years with the introduction of intraarterial and intravitreal chemotherapy. There is a trend to more conservative management and the challenge is to decide when to enucleate.MethodsWe have made a retrospective study of patients treated in 2013 and 2014.Unilateral retinoblastoma were treated by intraarterial melphalan and local treatments in selected cases and enucleation for advanced group D and for all group E eyes For bilateral retinoblastoma, conservative management was proposed with intravenous chemotherapy and local treatments Follow up every month under general anesthesia during the first year with treatment of small recurrences by laser or cryotherapy was performedResultsThere were 40 bilateral retinoblastoma and 4 of them were metachronous.19 patients received 6 courses of 3 drugs and 21 received two courses of VP16 and carboplatin followed by carboplatin. All the children had local ophthalmological treatments started at the third cycle. 21 children kept both eyes and 19 kept one eye. There were 72 unilateral retinoblastoma .43 (60%) were treated with primary enucleation and 29 (40%) were treated by conservative management. 21 of these eyes were saved and 8 were secondary enucleated. No patient developed orbital recurrence, optic nerve involvement or metastasis.ConclusionsThe increase of conservative management in retinoblastoma is safe with proper selection of eyes and close follows up.

Successful Treatment of Multisystem Langerhans Cell Histiocytosis (Histiocytosis X) with Etoposide

Langerhans cell histiocytosis (LCH) in its disseminated form usually occurs in the very young, and has a fulminant, rapidly progressive, and fatal course despite different forms of therapy. We treated two patients, who had failed on vinblastine treatment, with i.v. etoposide (VP-16) at a dose of 150 mg/kg/day for 3 days. Patient I, 8 months of age, presented with failure to thrive and huge bilateral granulomatous lesions of the external auditory canal with erosion and extensive destruction of the petrous pyramids and mastoid area. Patient II, 20 months of age, presented with widespread purpuric skin rash, hepatosplenomegaly, and bone marrow involvement. Both patients sustained complete remission (CR) following three to six courses of VP-16 and continued to be in unmaintained CR for > 48 months from diagnosis. No major toxicity was noted. Etoposide (VP-16), an epipodophyllotoxin known for its usefulness in the treatment of malignancies of the monocyte/macrophage lineage, appears to be an effective treatment for the severe multisystem (disseminated) LCH of childhood and should be strongly considered as front-line therapy for this subgroup of patients with poor prognostic factors.

High-Dose Carboplatinum and VP-16 in Treatment of Metastatic Adrenal Carcinoma

We describe a case of a patient that presented to our center with Cushing syndrome and was found to have an extensive metastatic adrenal carcinoma. He underwent debulking of the abdominal disease followed by eight courses of VP-16/carboplatinum. The patient had a remarkable response and is currently alive and in complete remission.

Response of osteogenic sarcoma to the combination of etoposide and cyclophosphamide as neoadjuvant chemotherapy

A Phase II study of the combination of etoposide (VP-16) and cyclophosphamide (CPM) was conducted in an attempt to identify active and potentially less toxic agents for treating patients with osteogenic sarcoma (OS). VP-16 was given as a 72-hour infusion for a total dose of 600 mg/m2. CPM was given as six pulses of 300 mg/m2 every 12 hours for a total dose of 1800 mg/m2. Seventeen newly diagnosed patients, including five (29%) with metastatic disease, were evaluated before and after two courses of VP-16 and CPM for clinical, radiologic, and biochemical (serum alkaline phosphatase [SAP]) responses of the primary tumor and metastases. Fifteen (88%) patients achieved complete or partial clinical responses. Fourteen (82%) patients achieved radiologic responses. Thirteen (87%) of 15 patients with higher than normal SAP levels for their age showed partial or complete responses. Three (60%) of the five patients with metastatic disease achieved complete or partial responses. The only major toxicity was myelosuppression, which led to 21 (62%) brief admissions after 34 courses of chemotherapy for intravenous antibiotic therapy for fever and neutropenia, without associated mortality. It was concluded that the combination of VP-16 and CPM is effective chemotherapy for both primary and metastatic OS. Although myelosuppression is inevitable, it is rapidly reversible in the drug dosages used. Further studies are needed to evaluate the effect of these drugs in combination with established agents in improving the disease-free survival of patients with OS.

Nichttestikuläre Keimzelltumoren: Analyse der Therapiestudie MAKEI 83/86 und Protokolländerungen für die Nachfolgestudie

205 patients with germ cell tumors were entered into the GPO Cooperative Study MAKEI 83/86 and classified as follows: 97 teratomas, 66 yolk sac tumors, 22 dysgerminomas, 17 embryonal carcinomas and three choriocarcinomas; 20% of all tumors were classified as mixed histology. Predominant primary sites were the ovaries (91 pts), the saccrococcygeal region (74 pts), the mediastinum (12 pts), the peritoneal cavity (10 pts) and other sites (18 pts). The treatment of teratomas was primarily surgery. Localised dysgerminomas received radiotherapy following surgery, in advanced stages (III, IV) four courses of chemotherapy vinblastine 3 mg/m2/day (days 1 + 2), bleomycin 15 mg/m2/day (days 1-3) and cisplatinum 20 mg/m2/day (days 4-8) (VBC) were applied. The other fully malignant tumors received four courses of VBC chemotherapy, in extragonadal primary tumors and advanced stages of all sites additional four courses of VP16 100 mg/m2/day (days 1-3), ifosfamide 1500 mg/m2/day (days 1-5) and cisplatin 20 mg/m2/day (days 1-5) (VPIC) were administered. To avoid mutilating surgery in advanced disease, four courses of VBC chemotherapy were administered prior to resection. The relapse-free survival according to Kaplan-Meier for protocol patients with teratomas is 0.97 +/- 0.01, for dysgerminomas 0.73 +/- 0.09 and for other fully malignant histologic entities 0.81 +/- 0.02 with a median period of observation of 31 months. The toxicity mainly consisted of myelosuppression during VPIC chemotherapy in 39 of 62 pts resulting in twelve incidents of sepsis with lethal outcome in two pts. Impaired renal function was reported in 14 pts, the incidence of neuropathy, ototoxicity and pulmonary toxicity was negligible. For the follow-up study a reduction in chemotherapy seems justified in patients with favourable prognosis. The substitution of VP16 for vinblastine may result in reduced toxicity.

The effect of dose of thoracic irradiation on recurrence in patients with limited stage small cell lung cancer. Initial results of a canadian multicenter randomized trial

Patients with limited stage small cell lung cancer were initially randomized to receive either three courses of Cyclophosphamide, Adriamycin, and Vincristine (CAV) followed by three courses of VP-16 and Cis-platin (VP-PT) or six courses of alternating CAV and VP-PT. Responding patients received prophylactic cranial radiation (PCI) after three courses of chemotherapy (CT) and loco-regional thoracic radiation (LRTR) after six courses. No maintenance chemotherapy was given. Patients receiving LRTR were randomized to receive either 25 Gy in ten fractions over 2 weeks (SD) or 37.5 Gy in 15 fractions over 3 weeks (HD). In both arms the pre-chemotherapy disease was treated with a 2 cm margin around the primary tumor volume. The mediastinum was included in the treatment volume and the supraclavicular nodes were also included if involved originally. The spinal cord was shielded after 32 Gy. Of the 333 patients enrolled by the time the trial closed in October 1984, 168 were eventually randomized to LRTR and are eligible for response assessment. The overall response rate after combined RT and CT was 94% (CR 67%, PR 27%). The CR rate for SD was 65% and for HD 69%. The combined treatment was well tolerated by most patients. Forty-nine percent of HD patients developed dysphagia compared to 26% of those SD ( p < 0.01). At the time of this analysis the median duration of follow-up since randomization to radiotherapy is 30 months. The median local progression-free survival on HD is 49 weeks. On SD it is 38 weeks ( p = 0.05, one sided). The actuarial incidence of local progression by 2 years is 69% on HD and 80% on LD. There is as yet no significant difference in overall survival between the two arms. It appears that HD radiotherapy as administered in this study may haev an impact on local control, but it is too early to determine if this will translate into a survival benefit.

Combined etoposide and 5-azacitidine in children and adolescents with refractory or relapsed acute nonlymphocytic leukemia: a Pediatric Oncology Group Study.

An intensive regimen of combined etoposide (VP-16) and 5-azacitidine (5-Az) was used to treat 96 children and adolescents with refractory or relapsed acute nonlymphocytic leukemia (ANLL). Patients were given two sequential five-day courses of VP-16, 250 mg/m2 for three days, followed by 5-Az, 300 mg/m2 for two days. An additional five-day course was administered if marrow aplasia was not evident by day 13. A complete remission rate of 45% was achieved with a median of two courses of VP-16 and 5-Az. The outcome of induction therapy was not influenced by prior treatment, blast cell morphology, or disease status on study entry (refractory or relapsed). Twenty-seven patients have relapsed after remission periods of 35 to 920 days (median, 110 days); seven others are free of leukemia for up to 519 days. The effectiveness of VP-16/5-Az combination therapy in patients refractory to anthracyclines and cytarabine indicates a potential role for these compounds in first-line treatment of patients with ANLL.

A Case of Adenocarcinoma of the Lung which Was Successfully Treated by Chemotherapy with Patient Survival without Recurrence for More Than Three Years

A 63-year-old man was admitted to the National Cancer Center Hospital on December 20, 1983 for a close examination of the abnormal shadows found in chest roentgenograms. Chest radiographs showed a massive right pleural effusion, a large tumor in the right hilar region and swelling of the left hilar nodes. Transcutaneous needle biopsy revealed the tumor's cytological type to be adenocarcinoma. The clinical stage was considered to be T3N2M1 (American joint committee (AJC) stage III M1), and his performance status was 4, so he was given etoposide (VP-16) alone as the initial chemotherapy treatment. He showed a partial response upon two courses of VP-16 therapy. Subsequently, one course of cisplatin (80 mg/m2) + vindesine (3.3 mg/m2), two courses of VP-16 (80 mg/m2 D1-4), five courses of cyclophosphamide (80 mg/m2) + adriamycin (50 mg/m2) + vincristine (1.4 mg/m2) and two courses of VP-16 (100 mg/m2 D1, 3, 5) were administered sequentially until May 31, 1985. No radiation therapy was given and, up to March 31, 1987, no sign of recurrence had been observed.