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Oncologist 1999;4(1):34-44 Related Articles, Links
Rhabdomyosarcoma: an overview.
Dagher R, Helman L.
Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Rhabdomyosarcoma (RMS) is a malignant tumor of mesenchymal origin thought to arise from cells committed to a skeletal
muscle lineage. With approximately 250 cases diagnosed yearly in the United States, it is the third most common extracranial
solid tumor of childhood after Wilms' tumor and neuroblastoma. Important epidemiologic, biologic, and therapeutic differences
have been elucidated within the RMS family. Common sites of primary disease include the head and neck region, genitourinary
tract, and extremities. A site-based tumor-nodes-metastasis staging system is being incorporated into use for assessing prognosis
and assigning therapy in conjunction with the traditional surgicopathologic clinical grouping system. The development of intensive
multimodality treatment protocols tested in large-scale international trials has resulted in significant improvements in outcome,
especially for patients with local or locally extensive disease for whom a 60%-70% disease-free survival can be expected.
Despite aggressive approaches incorporating surgery, dose-intensive combination chemotherapy, and radiation therapy, the outcome
for patients with metastatic disease remains poor. Future challenges include the development of less toxic therapy for patients
with localized disease and new approaches for patients with metastatic disease.
Publication Types:
• Review
• Review, Tutorial
PMID: 10337369 [PubMed - indexed for MEDLINE]
Arch Dis Child 2003 Apr;88(4):354-7 Related Articles, Links
Update on childhood rhabdomyosarcoma.
McDowell HP.
RLC NHS Trust Alder Hey, Liverpool, UK Dr H P McDowell, Consultant Paediatric Oncologist, RLC NHS Trust Alder Hey, Eaton
Road, Liverpool L12 2AP, UK. Heather.McDowell@RLCH.NWEST.NHS.UK
The overall survival of childhood rhabdomyosarcoma has improved dramatically over the past 10 years. Early diagnosis and
appropriate referral to a specialised centre leading to an accurate and timely diagnosis reflects on overall outcome. Recent
molecular studies have identified different biological subtypes resulting in the recognition of poorer subgroups and allowing
more appropriate treatment to be administered. Clinical trials remain the cornerstone to further improve outcome, now carried
out on an international basis.
Publication Types:
• Review
• Review, Tutorial
PMID: 12651771 [PubMed - indexed for MEDLINE]
Tohoku J Exp Med 2002 Dec;198(4):251-8 Related Articles, Links
Successful treatment for rhabdomyosarcoma by total spondylectomy in a child.
Saito T, Aizawa T, Kashimoto O, Sato T, Kokubun S.
Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai 980-8574, Japan.
A 7-year-old girl with a retroperitoneal rhabdomyosarcoma having invaded the L3 vertebra was treated by combination therapy
consisting of chemotherapy, surgical resection and intraoperative radiation. Surgically, total spondylectomy was performed
through a combined anterior and posterior procedures, and the spine was reconstructed with fibula bone grafts using a pedicle
screw system made of titanium alloy. Transverse junction plates were not used at operation because of their bulkiness for
the patient. Five days postoperatively, the rods dislodged from the screws and the grafted bones leaned. A Chance fracture-like
transverse fracture of the L4 vertebra occurred during the revisional operation. Transverse plates and sublaminar wires were
used to reduce the fracture and achieved stability. Six years postoperatively, the spine was completely fused and no local
recurrence or metastasis is detected.
PMID: 12630557 [PubMed - in process]
Cancer Res 2003 Apr 1;63(7):1508-14 Related Articles, Links
Potent Oncolytic Activity of Multimutated Herpes Simplex Virus G207 in Combination with Vincristine against Human Rhabdomyosarcoma.
Cinatl J Jr, Cinatl J, Michaelis M, Kabickova H, Kotchetkov R, Vogel JU, Doerr HW, Klingebiel T, Driever PH.
Institute of Medical Virology, Center of Hygiene, D-60596 Frankfurt am Main, Germany [Ji. Cinatl, Ja. Cinatl, M. M., R.
K., J-U. V., H. W. D.].
Replication restricted oncolytic viruses such as multimutated herpes simplex virus type 1 (HSV-1) G207 represent a novel
and attractive approach for cancer therapy, including pediatric solid tumors. Rhabdomyosarcoma is the most common soft-tissue
sarcoma of childhood and is often diagnosed already as an advanced disseminated disease. Despite aggressive therapeutic approaches,
the prognosis for patients with metastatic rhabdomyosarcoma remains grim. Therefore, there is a need for novel effective drugs
with superior safety and efficacy profile. In this study, we showed marked in vitro activity of HSV-1 G207 against embryonal
and alveolar rhabdomyosarcoma cells. All human embryonal (KF-RMS-1, RD, and CCA) and alveolar RMS (KFR, Rh28, Rh30, and Rh41)
cell lines were highly sensitive to cytotoxic and replicative effects of G207 even at a multiplicity of infection of 0.01,
except embryonal Rh1 rhabdomyosarcoma cells, which were efficiently killed only upon multiplicity of infection of 1.0. i.v.
G207 treatment of xenotransplanted KFR and KF-RMS-1 tumors in mice led to significant tumor growth inhibition of both tumor
entities, whereas intraneoplastic G207 treatment additionally resulted in complete tumor disappearance in 25% of animals.
No difference has been found between alveolar and embryonal types of rhabdomyosarcoma. Combination treatment of both cell
lines with G207 and vincristine led to strongly enhanced in vitro cytotoxicity without affecting infection efficiency and
replication of G207 in KFR as well as in KF-RMS-1 cells. In vivo combination treatment using i.v. G207 and vincristine resulted
in complete regression of alveolar rhabdomyosarcoma in five of eight animals and significant growth inhibition of embryonal
rhabdomyosarcoma. Taking into consideration the proven safety of G207 in humans, we suggest that G207 alone and in combination
with vincristine should be additionally evaluated as a potential agent against human rhabdomyosarcoma.
PMID: 12670897 [PubMed - in process]
J Clin Oncol 2003 Jan 1;21(1):78-84 Related Articles, Links
Prognostic factors and clinical outcomes in children and adolescents with metastatic rhabdomyosarcoma--a report from the
Intergroup Rhabdomyosarcoma Study IV.
Breneman JC, Lyden E, Pappo AS, Link MP, Anderson JR, Parham DM, Qualman SJ, Wharam MD, Donaldson SS, Maurer HM, Meyer
WH, Baker KS, Paidas CN, Crist WM.
Children's Hospital Medical Center, Division of Radiation Oncology, Cincinnati, OH 45219-0757, USA. brenemjc@healthall.com
PURPOSE: To identify risk factors associated with outcomes in children with metastatic rhabdomyosarcoma (RMS) treated
on the fourth Intergroup Rhabdomyosarcoma Study (IRS-IV). PATIENTS AND METHODS: Patients with metastatic RMS were treated
with one of two regimens that incorporated a window of either ifosfamide and etoposide (IE) with vincristine, dactinomycin,
and cyclophosphamide (VAC) or vincristine, melphalan (VM) and VAC. Study end points were failure-free survival (FFS) and overall
survival (OS). Clinical factors including age, histology, sites of primary and metastatic disease, and number of sites of
metastatic disease were correlated with those end points. RESULTS: One hundred twenty-seven patients were eligible for analysis.
The estimated 3-year OS and FFS for all patients were 39% and 25%, respectively. By univariate analysis, 3-year OS was significantly
influenced by histology (47% for embryonal v 34% for all others, P =.026) and increasing number of metastatic sites (P =.028).
By multivariate analysis, the presence of two or fewer metastatic sites was the only significant predictor (P =.007 and.006,
respectively). The combination of embryonal histology with two or fewer metastatic sites identified a subgroup with 3-year
FFS of 40% and OS of 47%. CONCLUSION: Children with group IV RMS treated on the IRS-IV study had improved OS and FFS if they
had two or fewer metastatic sites and embryonal histology. This favorable subset of patients has outcomes approaching those
observed in selected patients with localized, nonmetastatic disease. Thus, these patients might not be appropriate candidates
for regimens that include experimental agents with substantial toxicities or unproven antitumor activity.
PMID: 12506174 [PubMed - indexed for MEDLINE]
Cancer 2003 Apr 15;97(8):1974-80 Related Articles, Links
Role of surgery for nonmetastatic abdominal rhabdomyosarcomas.
Cecchetto G, Bisogno G, Treuner J, Ferrari A, Mattke A, Casanova M, Dall'Igna P, Zanetti I, Volpato S, Siracusa F, Scarzello
G, Boglino C, Carli M.
Department of Pediatrics, Division of Pediatric Surgery, University of Padua, Padua, Italy.
BACKGROUND: In the current study, the authors aim to evaluate clinical features and treatment results observed in patients
from the German and Italian studies who had nonmetastatic abdominal rhabdomyosarcomas (RMS). METHODS: One hundred sixty-one
patients were observed; 78 registered in the German studies between October 1980 and August 1995, and 83 registered in the
Italian studies between April 1975 and December 1995. The age range of the patients was 0-18 years (median, 4 yrs). The distribution
of tumor sites was as follows: 32 intraperitoneal, 42 retroperitoneal, 75 pelvic, and 12 not otherwise specified (NOS). Most
patients had a large and invasive primary mass (26 T1b, 114 T2b). The breakdown in histology was as follows: 116 embryonal,
34 alveolar, and 11 other (leiomyomatous, pleomorphic, and NOS); all cases were staged according to the Intergroup Rhabdomyosarcoma
Studies (IRS) system. Nine Group I patients were treated after surgery with chemotherapy (CT) (radiotherapy [RT] was delivered
to treat alveolar RMS in the 1991 German and 1988 Italian studies); 19 Group II patients received CT + RT (40-44 Gy); 133
Group III patients underwent neoadjuvant CT +/- surgery and/or RT (54 Gy) + CT. Different CT regimens (based primarily on
the administration of vincristine, dactinomycin, doxorubicin, and cyclophosphamide or ifosfamide) were adopted. RT was not
recommended for patients age < 3 years. RESULTS: The 10-year overall survival (OS) and progression-free survival (PFS)
were 47.2% and 43.9%, respectively. The OS was related significantly to the following variables: histology (alveolar, 29.4%
vs. nonalveolar, 52.1% [P = 0.0156]), tumor size (> 5 cm, 42.1% vs. < 5 cm, 81% [P = 0.005]), age (< 10 yrs, 51.4%
vs. >/= 10 yrs, 27.8% [P = 0.02]), complete surgery at diagnosis or after CT (+/-RT) (70.4% vs. 34.4% without it [P = 0.0015]).
Most patients who achieved the delayed local control had responded well to neoadjuvant CT. CONCLUSIONS: Tumor size, histology,
age, and initial or delayed achievement of local control were important prognostic factors. Most relapsed patients had unfavorable
outcomes. Cancer 2003;97:1974-80. Copyright 2003 American Cancer Society.DOI 10.1002/cncr.11285
PMID: 12673726 [PubMed - in process]
Cancer 2003 Jan 1;97(1):179-85 Related Articles, Links
Long-term results of three-dimensional conformal radiation therapy for patients with rhabdomyosarcoma.
Wolden SL, La TH, LaQuaglia MP, Meyers PA, Kraus DH, Wexler LH.
Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, SM07, New York, NY 10021,
USA. woldens@mskcc.org
BACKGROUND: The authors evaluated the outcome of patients with rhabdomyosarcoma (RMS) who were treated with three-dimensional
(3D) conformal radiation therapy (RT) at a single institution. METHODS: The records of all 69 patients with RMS who received
3D RT from 1989 to 2001 were reviewed. All patients received multiagent chemotherapy with or without surgical resection. Follow-up
of surviving patients ranged from 1.0 year to 12.8 years (median, 4.3 years). RESULTS: The median patient age was 6 years
(range, 1-29 years), and there was a male:female ratio of 1.5:1. Forty-eight patients had embryonal sarcomas, 14 patients
had alveolar sarcomas, and 7 patients had undifferentiated sarcomas. The parameningeal area (n = 22 patients) and the trunk
(n = 21 patients) were the most common sites. Twelve percent of patients had Stage I disease, 10% of patients had Stage II
disease, 51% of patients had Stage III disease, and 27% of patients had Stage V disease. Nine percent of patients were in
clinical Group II, 64% of patients were in Group III, and 27% of patients were in Group IV. Regional lymph nodes were involved
in 33% of patients, and 77% of tumors measured > or = 5 cm in greatest dimension. The actuarial 5-year local and regional
control rates were 90% and 91%, respectively. No predictive factors for local failure were identified; however, alveolar histology
was correlated with regional recurrence (29% compared with 4%; P = 0.02). The disease free and overall survival rates were
60% and 63% at 5 years, respectively. Disease stage was most predictive of 5-year survival (76% of patients with Stage I-III
disease compared with 24% of patients with Stage IV disease; P < 0.001). CONCLUSIONS: High rates of local control were
achieved in patients with RMS using 3D RT. Regional lymph node failure was increased significantly among patients with alveolar
histology. Control of metastatic disease remains a formidable problem for patients with Stage IV RMS. Copyright 2002 American
Cancer Society.
PMID: 12491519 [PubMed - indexed for MEDLINE]
Cancer 2002 Sep 15;95(6):1354-65 Related Articles, Links
Peripheral blood stem cell support reduces the toxicity of intensive chemotherapy for children and adolescents with metastatic
sarcomas.
Hawkins DS, Felgenhauer J, Park J, Kreissman S, Thomson B, Douglas J, Rowley SD, Gooley T, Sanders JE, Pendergrass TW.
Department of Pediatrics, Children's Hospital and Regional Medical Center, Seattle, Washington 98105, USA. dhawki@chmc.org
BACKGROUND: To increase the dose intensity (DI) of chemotherapy for pediatric patients with metastatic sarcomas, including
the Ewing sarcoma family of tumors (ESFT) and rhabdomyosarcoma (RMS), the authors tested the feasibility of an intensive regimen
supported by granulocyte-colony stimulating factor (G-CSF) and peripheral blood stem cells (PBSC). METHODS: Twenty-three children
and adolescents with metastatic sarcomas received vincristine, doxorubicin, cyclophosphamide, ifosfamide, sodium mercaptoethanesulfonate
(mensa), and etoposide (VACIME) chemotherapy, consisting of 8 courses of vincristine 2 mg/m(2) on Day 0, doxorubicin 37.5
mg/m(2) per day on Days 0-1, cyclophosphamide 360 mg/m(2) per day on Days 0-4, ifosfamide 1800 mg/m(2) per day on Days 0-4,
mesna 2400 mg/m(2) per day, and etoposide 100 mg/m(2) per day on Days 0-4. Doxorubicin was omitted in Courses 7 and 8. G-CSF
was given after each course of therapy. Courses of therapy were repeated every 21 days or as soon as hematopoietic recovery
permitted. PBSC were collected twice: first, after Course 2 (infused after Courses 3 and 4) and, second, after Course 4 (infused
after Courses 5 and 6). Surgical resection followed Course 6, and radiotherapy followed Course 8. RESULTS: PBSC collections
were adequate in 91% of all harvests. The mean DI was 82% (standard deviation, 14%) of the intended DI, which was greater
than historic data without PBSC support. Seventeen patients (74%) achieved a complete response (CR), 12 patients with chemotherapy
alone and 5 more patients after undergoing surgical resection. Fifteen patients developed progressive disease, with a 2-year
event free survival (EFS) rate of 39% (95% confidence interval, 19-59%). Hematopoietic toxicity was severe and cumulative,
although it was less than that seen previously without PBSC support. CONCLUSIONS: PBSC-supported multicycle chemotherapy is
a feasible method to increase chemotherapy DI for pediatric patients with metastatic sarcomas. Although the CR rate compared
favorably with previously reported response rates, the 2-year EFS rate was similar to that achieved with other intensive regimens.
Copyright 2002 American Cancer Society.
PMID: 12216105 [PubMed - indexed for MEDLINE]
Crit Rev Oncol Hematol 2002 Feb;41(2):191-6 Related Articles, Links
High-dose chemotherapy in soft tissue sarcoma in children.
Atra A, Pinkerton R.
Department of Paediatric Oncology, The Royal Marsden Hospital NHS Trust/Institute of Cancer Research, Downs Road, Sutton,
SM2 5PT, Surrey, UK.
Soft tissue sarcomas (STS) are highly malignant tumours that constitute 5-6% of all malignant childhood neoplasms. Of
these, rhabdomyosarcoma (RMS) is the most common in children, and has a characteristic two-peak age incidence, 2-5 and 15-19
years. Most children with RMS are cured with conventional chemotherapy and local therapy (surgery with or without radiotherapy).
Children with metastatic disease at presentation, particularly those older than 10 years or with bone marrow or bone involvement
have a much poorer outcome. In this subgroup, high-dose therapy with stem cell rescue has been studied over the last two decades.
Various single or multiagent chemotherapy regimens with or without radiotherapy and autologous stem cell rescue have been
used as consolidation treatment with little success. Recent trials using sequential high-dose chemotherapy in the early phase
of treatment have proved to be feasible, but the beneficial effect has to be confirmed. The role of purging remains unclear.
Collaboration between different international groups is urgently required, in an attempt to improve the poor outcome of children
with high risk STS.
Publication Types:
• Review
• Review, Tutorial
PMID: 11856594 [PubMed - indexed for MEDLINE]
J Pediatr Hematol Oncol 2001 May;23(4):225-33 Related Articles, Links
Comment in:
• J Pediatr Hematol Oncol. 2001 Aug-Sep;23(6):334-7.
#
Ifosfamide and etoposide are superior to vincristine and melphalan for pediatric metastatic rhabdomyosarcoma when administered
with irradiation and combination chemotherapy: a report from the Intergroup Rhabdomyosarcoma Study Group.
Breitfeld PP, Lyden E, Raney RB, Teot LA, Wharam M, Lobe T, Crist WM, Maurer HM, Donaldson SS, Ruymann FB.
Intergroup Rhabdomyosarcoma Study Group, Children's Cancer Group, Arcadia, California, USA. breit003@mc.duke.edu
PURPOSE: This study was designed to estimate the partial and complete response rates (CR and PR) of two novel drug pairs
(vincristine and melphalan vs. ifosfamide and etoposide) and to improve overall survival of previously untreated patients
with metastatic rhabdomyosarcoma. PATIENTS AND METHODS: One hundred twenty-eight patients were randomly assigned to phase
II window therapy consisting of vincristine and melphalan (VM-containing regimen) or ifosfamide and etoposide (IE-containing
regimen). Brief window therapy (12 wks) was immediately followed-up by vincristine, dactinomycin, and cyclophosphamide (VAC),
chemotherapy, surgery, and irradiation, with continuation of either VM or IE in patients with initial response. Major endpoints
were initial CR and PR rates after the phase II window phase of therapy, failure-free survival (FFS), and survival. RESULTS:
Patients who received the VM-containing regimen experienced significantly more anemia, neutropenia, thrombocytopenia, and
had more cyclophosphamide dose reductions. The initial PR and CR rates were not significantly different for patients treated
with either regimen (VM, 74%; IE, 79%; P = 0.428). However, FFS and overall survival (OS) at 3 years were significantly better
with the IE-containing regimen (FFS: 33% vs. 19%; P = 0.043; OS: 55% vs. 27%; P = 0.012). CONCLUSIONS: Although the VM-containing
regimen produced a high response rate, inclusion of melphalan appeared to limit the cyclophosphamide dose that could be administered,
and ultimately, this regimen was associated with a significantly worse outcome than was the IE-containing regimen. Also, the
IE-containing regimen was associated with a gratifyingly high survival rate at 3 years (55%), which is significantly higher
than has been observed on any previous Intergroup Rhabdomyosarcoma Study Group regimen for similar patients. We believe that
this promising outcome indicates that this drug pair merits further randomized testing in metastatic rhabdomyosarcoma.
Publication Types:
• Clinical Trial
• Clinical Trial, Phase II
• Multicenter Study
• Randomized Controlled Trial
PMID: 11846301 [PubMed - indexed for MEDLINE]
Cancer 1993 Mar 1;71(5):1904-22 Related Articles, Links
The Intergroup Rhabdomyosarcoma Study-II.
Maurer HM, Gehan EA, Beltangady M, Crist W, Dickman PS, Donaldson SS, Fryer C, Hammond D, Hays DM, Herrmann J, et al.
Medical College of Virginia/Virginia Commonwealth University, Richmond 23298.
BACKGROUND. Intergroup Rhabdomyosarcoma Study (IRS)-II, (1978-1984) had the general goals of improving the survival and
treatment of children with rhabdomyosarcoma (RMS). METHODS. Nine hundred ninety-nine previously untreated eligible patients
entered the study after surgery and were randomized or assigned to therapy by IRS Clinical Group (I-IV), tumor site, and histologic
type. Outcomes were compared between treatments and with results of IRS-I (1972-1978). RESULTS. Patients in Group I, excluding
extremity alveolar (EA) RMS, were randomized to standard vincristine (V), dactinomycin (A), and cyclophosphamide (C) or standard
VA. At 5 years, disease-free survival (DFS) and survival (S) rates were similar between VAC and VA (DFS: 80%, 70%, P = 0.47;
S: 85%, 84%, P = 0.73). Patients in Group II, excluding EA RMS, received radiation and were randomized to intensive VA or
repetitive-pulse VAC. Outcomes were similar for rates of DFS (69%, 74%, P = 0.83) and S (88%, 79%, P = 0.17). Patients in
Group III, excluding certain pelvic tumors, received radiation and were randomized to repetitive-pulse VAC or repetitive-pulse
VAdrC-VAC (Adr, Adriamycin [doxorubicin]). Complete remission (CR) rates were close at 74%, 78%, respectively (P = 0.32),
as were percentages in CR (73%) and S (66%) rates; the latter outcomes were significantly better than IRS-I (CR: 56%, P <
0.001; S: 50%, P < 0.001). Central nervous system prophylaxis for Group III patients with cranial parameningeal sarcoma
increased S rate to 67% from 45% in IRS-I (P < 0.001). Patients in Group IV received the same regimens as Group III; the
CR rate was 53%, 38% remained in CR and S rate was 27% with and 26% without Adr (P = 0.90). At 5 years, S rate for IRS-II,
including EA and all pelvic tumors, was 63%: an 8% increase over IRS-I (P < 0.001). Outcomes by primary site were as good
as, or better than, the IRS-I experience. CONCLUSIONS. Combining all Groups and treatments in IRS-II, the major improvement
in S rate at 5 years between studies was in nonmetastatic patients (71% for IRS-II versus 63% for IRS-I, P = 0.01).
Publication Types:
• Clinical Trial
• Randomized Controlled Trial
PMID: 8448756 [PubMed - indexed for MEDLINE]
Med Pediatr Oncol 2001 Nov;37(5):442-8 Related Articles, Links
Efficacy of ifosfamide and doxorubicin given as a phase II "window" in children with newly diagnosed metastatic
rhabdomyosarcoma: a report from the Intergroup Rhabdomyosarcoma Study Group.
Sandler E, Lyden E, Ruymann F, Maurer H, Wharam M, Parham D, Link M, Crist W.
Intergroup Rhabdomyosarcoma Study Group Operations Office, Children's Oncology Group, Arcadia, CA 91066-6012, USA. smason@nccf.org
BACKGROUND: The cure rate for children/adolescents with localized rhabdomyosarcoma (RMS) has tripled over the past 25
years, but patients with metastatic disease at presentation have not benefited similarly, and urgently need new therapy. We
evaluated a new drug pair, ifosfamide + doxorubicin, for such patients. PROCEDURE: We estimated the complete and partial response
rates (i.e., CR and PR) of 152 previously untreated children/adolescents with metastatic RMS entered on the IRS-IV pilot from
July 1988 to October 1991 who received an "up-front window" of ifosfamide (1.8 gm/m(2)/day for 5 days) and doxorubicin
(30 mg/m(2)/day for 2 days) given every 3 weeks for 12 weeks. This was followed by combination chemotherapy with vincristine,
actinomycin D, and cyclophosphamide (VAC), given every 3 weeks for an additional 36 weeks. RESULTS: Of 115 patients evaluable
for early response at 12 weeks, 28 (20%) had CR and 66 (43%) had PR. The ultimate CR rate was 52%. Overall, about one-third
of patients survived. Prognostic factor analysis revealed that patients < 10 years old (P < 0.001), those with embryonal
tumors (P = 0.002), or a GU primary site (P = 0.010), and those who lacked nodal disease (P = 0.041), and those who lacked
bone or bone marrow metastasis (P < 0.001) fared better than did others. CONCLUSIONS: The 63% CR + PR rate achieved at
12 weeks and overall 5-year FFS seen with this drug pair is similar to that achieved with previously evaluated drug combinations.
We conclude that ifosfamide/doxorubicin is highly active in advanced RMS, and should be considered for inclusion in frontline
therapy for children with intermediate or high-risk RMS. Copyright 2001 Wiley-Liss, Inc.
Publication Types:
• Clinical Trial
• Clinical Trial, Phase II
• Multicenter Study
PMID: 11745872 [PubMed - indexed for MEDLINE]
Anticancer Res 1987 Jul-Aug;7(4B):861-7 Related Articles, Links
Decreased rat rhabdomyosarcoma pulmonary metastases in response to a low methionine diet.
Breillout F, Hadida F, Echinard-Garin P, Lascaux V, Poupon MF.
Centre National de la Recherche Scientifique, Institut de Recherche Sur le Cancer, Villejuif, France.
Many Experimental and human tumor cell lines have been previously described as being dependent upon exogenous methionine
for their in vitro proliferation. The rationale of the experiments described herein was to decrease the in vivo growth of
malignant tumors by reducing the exogenous methionine available in diets fed to Wistar AG rats bearing the highly metastatic
rhabdomyosarcoma, RMS-J1. The methionine content in the diet was reduced either by replacing casein (diet 1) with soybean
protein (diet 4), or by lowering the amount of soybean protein in the diet (from 23 g/100 g to 12 g/100g) (diet 5), or by
using a crystalline amino acid-defined mixture as the source of protein (diet 7). In the latter diet homocysteine replaced
methionine and allowed the survival of the animals. Diet 4 significantly reduced the mean number of lung metastases without
affecting the primary tumor growth. Treatment of RMS-J1 bearing rats with diet 5 led to the decrease of pulmonary invasion
(78 and 21 median lung metastases, respectively, in control and treated groups). This diminished metastatic dissemination
resulted from the reduced methionine consumption: the lowered casein content in diet 3 (10 g/100 g) as compared to diet 1
(23 g) did not alter primary tumor growth or the amplitude of lung invasion. Moreover, the addition of methionine to diet
5 prevented the diminution of the median number of lung metastases. Replacement of methionine with homocysteine in the crystalline
amino acid-defined mixture (diet 7) fed to RMS-J1 bearing rats led to a limited retardation of primary tumor growth (less
than 10%) and to a significant decrease in pulmonary invasion: the median number of pulmonary metastases was 28 and 9 for
control and treated rats respectively.
PMID: 3674775 [PubMed - indexed for MEDLINE]
J Nutr 1995 Mar;125(3 Suppl):698S-708S Related Articles, Links
Soy and experimental cancer: animal studies.
Hawrylewicz EJ, Zapata JJ, Blair WH.
Department of Research, Mercy Hospital and Medical Center, Chicago, IL 60616.
Studies are reviewed that report consumption of soy protein diets inhibits the growth of various tumors in rats. The inhibitory
effect has been attributed to the phytoestrogens (genistein and diadzein) or protein kinase inhibitor in soy protein products.
Recent studies indicate that additional factors in soy protein products may also contribute to the inhibition of tumorigenesis,
namely the deficiency of the essential amino acid methionine. Metastatic growth to the lungs of a primary rhabdomyosarcoma
tumor was inhibited by feeding a soy protein diet. The effect was reversed by methionine fortification of the diet. Carcinogen-induced
mammary tumor development was inhibited during the promotional phase in rats fed soy protein isolate diet and reversed with
a methionine-supplemented diet. Additional studies demonstrated that after excision of the primary mammary tumor, growth of
additional tumors was inhibited when the diet was changed from casein to soy protein isolate. Histopathologic evaluation of
the mammary tumors revealed more benign fibroadenomas and lower-grade adenocarcinomas in the soy protein group. Before carcinogen
administration (at 7 weeks of age), ornithine decarboxylase activity and polyamine concentrations in the rat mammary epithelium
were significantly lower in the soy protein group. These data suggest an inhibitory effect on mammary epithelial growth in
the soy-protein-fed group.
Publication Types:
• Review
• Review, Tutorial
PMID: 7884554 [PubMed - indexed for MEDLINE]
Carcinogenesis 1998 Mar;19(3):501-7 Related Articles, Links
Inhibition of spontaneous formation of lung tumors and rhabdomyosarcomas in A/J mice by black and green tea.
Landau JM, Wang ZY, Yang GY, Ding W, Yang CS.
Laboratory for Cancer Research, College of Pharmacy, Rutgers University, Piscataway, NJ 08854, USA.
We investigated the effects of black tea (BT) and green tea (GT) infusion on the spontaneous formation of lung tumors
and rhabdomyosarcomas in A/J mice. Female A/J mice, 6 weeks of age, were allocated into five groups (50 per group) and were
given the following as the sole source of drinking fluid: (i) deionized water (control group), (ii) 0.5% BT, (iii) 1% BT,
(iv) 2% BT and (v) 1% GT. After 60 weeks, the mice were killed by decapitation. Lung tumor incidence, multiplicity and volume
were significantly lower in the 2% BT group as compared with the controls (27 versus 52%, 0.33 versus 0.72 tumors/mouse and
4.27 versus 38.3 mm3, respectively). The 1% GT group had significantly lower lung tumor multiplicity (0.41/mouse), while the
1% BT group had significantly decreased tumor volume (7.17 mm3). Rhabdomyosarcomas were found in 34% of the mice in the control
group, and both the 1 and 2% BT groups had significantly lower incidences at 13 and 14%, respectively. The mice in the 2%
BT group weighed 16% less than those in the control group, although they consumed more food than the control group. The other
tea-consuming groups also weighed less than the control group (7.8-11%) while consuming more food and fluid. In a separate
experiment, similar carcinogenesis inhibition was also observed in female A/J mice that were given 0.6% and then 0.3% instant
black tea for 52 weeks. These results demonstrate the inhibitory activity of BT against the spontaneous formation of lung
tumors and rhabdomyosarcomas in mice.
PMID: 9525286 [PubMed - indexed for MEDLINE]
J Med Virol 2003 May;70(1):119-25 Related Articles, Links
Inhibition of enterovirus 71-induced apoptosis by allophycocyanin isolated from a blue-green alga Spirulina platensis.
Shih SR, Tsai KN, Li YS, Chueh CC, Chan EC.
School of Medical Technology, Chang Gung University, Tao-Yuan, Taiwan.
Enterovirus 71 infection causes significant morbidity and mortality in children, yet there is no effective treatment.
In this study, a protein-bound pigment, allophycocyanin purified from blue-green algae is first reported to exhibit anti-enterovirus
71 activity. Allophycocyanin neutralized the enterovirus 71-induced cytopathic effect in both human rhabdomyosarcoma cells
and African green monkey kidney cells. The 50% inhibitory concentration of allophycocyanin for neutralizing the enterovirus
71-induced cytopathic effect was approximately 0.045 +/- 0.012 microM in green monkey kidney cells. The cytotoxic concentrations
of allophycocyanin for rhabdomyosarcoma cells and African green monkey kidney cells were 1.653 +/- 0.003 microM and 1.521
+/- 0.012 microM, respectively. A plaque reduction assay showed that the concentrations of allophycocyanin for reducing plaque
formation by 50% were approximately 0.056 +/- 0.007 microM and 0.101 +/- 0.032 microM, when allophycocyanin were added at
the state of viral adsorption and post-adsorption, respectively. Antiviral activity was more efficient in cultures treated
with allophycocyanin before viral infection compared with that in the cultures treated after infection. Allophycocyanin was
also able to delay viral RNA synthesis in the infected cells and to abate the apoptotic process in enterovirus 71-infected
rhabdomyosarcoma cells with evidence of characteristic DNA fragmentation, decreasing membrane damage and declining cell sub-G1
phase. It is concluded that allophycocyanin possesses antiviral activity and has a potential for development as an anti-enterovirus
71 agent. Copyright 2003 Wiley-Liss, Inc.
PMID: 12629652 [PubMed - in process]
J Cancer Res Clin Oncol 1980;97(1):91-6 Related Articles, Links
Inhibition of benzo(a)pyrene carcinogenesis in rats with vitamin C.
Kallistratos G, Fasske E.
The s.c. infection of 10 mg benzo(a)pyrene dissolved in 1 ml tricaprylin induced in Wistar rats local malignant tumors,
such as fibrosarcoma, rhabdomyosarcoma, and polymorph cell sarcoma. The growth of the tumors was relatively rapid, reaching
weights of 140-155 g before rats died 142-168 days after the administration of the carcinogen. On the contrary, under the
same experimental conditions, high doses of Vitamin C about 525 mg/day/rat administered orally in drinking water (total amount
of Vitamin C 55 g/rat corresponding to 40% of their body weight ) inhibited to a great extent the benzo(a)pyrene carcinogenesis.
Only one slowly growing rhabdomyosarcoma (13 g of weight) was developed showing characteristic damage of malignant cells and
partial replacement of the neoplastic area with granuloma tissue. The significance ov Vitamin C for cancer prevention and
treatment is discussed.
PMID: 7400211 [PubMed - indexed for MEDLINE]
Int J Hyperthermia 1988 Nov-Dec;4(6):677-86 Related Articles, Links
Thermotolerance kinetics and growth rate changes in the R1H tumour heated at 43 degrees C.
Mooibroek J, Dikomey E, Zywietz F, Jung H.
Institute of Biophysics and Radiobiology, University of Hamburg, F.R.G.
R1H rhabdomyosarcomas implanted into the foot of the right hind leg of female WAG/Rij rats were exposed to fractionated
hyperthermia at 43 degrees C and the kinetics of thermotolerance and heat-induced growth rate changes were studied. Tumours
of anaesthetized animals were exposed to heat by immersing the leg up to the thigh in a water bath. Tumour growth delay (TGD)
and tumour volume doubling time were calculated from individual growth curves. After single heating, TGD increased with increasing
heating time, the increase being linear for heating times exceeding 60 min. Thermotolerance was induced by a priming heat
treatment at 43 degrees C for 60 min and the kinetics of development and decay was studied for fractionation intervals ranging
from 4 to 144 h. After 4 h the thermal sensitivity of the tumours was enhanced by about 30 per cent, probably due to the sensitizing
effect of heat-induced physiological alterations in the tumour tissue such as suboptimal environmental conditions caused by
depressed blood flow. For longer time intervals thermotolerance developed and reached a maximum at 24 h where the thermotolerance
ratio was 4.5 +/- 1.5. From 24 to 144 h thermotolerance decayed exponentially with a half-time of 28 +/- 8 h. Heat also affected
the growth rate of the treated tumours. After single heat treatments at 43 degrees C for 15-60 min the tumours grew faster
than untreated control tumours. This change was statistically significant. After prolonged single heating, growth rate was
found to be reduced. Tumour volume doubling time was not detectably changed after fractionated heat treatments.
PMID: 3171262 [PubMed - indexed for MEDLINE]
Cancer Immunol Immunother 1987;25(2):111-8 Related Articles, Links
Antimetastatic effect of immunomodulators from Nocardia opaca in mice and rats activation of peritoneal macrophages by
these fractions.
Barot-Ciorbaru R, Cornil I, Grand-Perret T, Poupon MF.
Universite Paris-Sud, Institut de Biochimie, Orsay, France.
Nocardia delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, injected i.p. in an oil/water
emulsion to F6 rhabdomyosarcoma-bearing rats, inhibited the development of pulmonary metastases; 6 out of 10 rats were protected.
Repeated i.p. administration of emulsified NDCM and of two other compounds, a Nocardia water soluble mitogen (NWSM a hydrosoluble
fraction) and purified cell walls (CW, an insoluble macromolecular fraction) in Lewis lung carcinoma (LLC)-bearing mice resulted
in a significant reduction of lung metastases. The efficiency of these fractions was enhanced by association with monokines.
A combination regimen of NDCM, NWSM, and CW (100 micrograms/0.1 ml) and monokines (0.1 ml), injected i.p. in LLC-bearing mice,
yielded a greater antimetastatic effect than either therapy alone. Peritoneal macrophages from mice which had been injected
i.p. with NWSM or CW, when triggered either by TPA (tetradecanoyl phorbol acetate) or by zymosan, released large quantities
of hydrogen peroxide and had a high rate of glucose consumption. These macrophages were activated as judged by their cytostatic
activity against syngeneic P815 mastocytoma growth; they expressed biochemical markers which have been reported to characterize
the activated state. Incubation of thioglycollate-elicited peritoneal macrophages with NWSM, and monokines for 72 h resulted
in a cytotoxic activity against labeled LLC cells; addition of macrophage activating factor significantly increased the cytotoxic
capacity of these macrophages. In view of this we postulate that the antimetastatic effect of soluble and insoluble N. opaca
fractions and monokines might be mediated by activated peritoneal macrophages.
PMID: 3117366 [PubMed - indexed for MEDLINE]
Int J Immunopharmacol 1994 May-Jun;16(5-6):475-80 Related Articles, Links
Antitumoral activity of an immunomodulatory fraction of Nocardia opaca: mechanism of action.
Leibovici J, Hoenig S, Pinchassov A, Barot-Ciorbaru R.
Department of Pathology, Sackler Faculty of Medicine, Tel-Aviv University, Israel.
Immunomodulatory substances have been used as antineoplastic agents in experimental and human systems. Many of these agents
were derived from microorganisms. Several biologically active fractions have been isolated from Nocardia. These derivatives
were shown to induce interferon production, to activate natural killer cells and macrophages and to exert an antitumoral effect.
We attempted to examine the mechanism of the antitumoral activity of the Nocardia water-soluble mitogen (NWSM). The tumor
tested was the Lewis lung carcinoma (3LL). Regular histological examination and identification of the cellular immune reaction
by monoclonal antibodies against macrophages (Mac 1 antigen), B- (IgG expressing) and T-lymphocytes (anti-Lyt-1), analysed
by flow cytometry, were performed on samples of the tumor site and of the spleen. Intratumoral administration of the immunomodulators
resulted in a massive accumulation of inflammatory cells around the tumor in mice treated with NWSM. The thick rim of infiltrating
cells consisted of macrophages and lymphocytes, while the nontreated tumor was found to provoke only a scanty lymphocyte infiltration.
Macrophages were, therefore, present at the tumor site and were directly implicated in the antitumoral effect of the Nocardia
immunomodulator. T-lymphocytes were also observed at the site of the tumor. The spleen reaction consisted of marked extramedullary
hematopoiesis and enlarged follicles containing prominent germinal centres (assessed also by a FACS-demonstrated increase
in B-lymphocytes). In view of the inefficiency of chemotherapy in the treatment of advanced cancer, it is of major importance
to explore alternative cancer treatment modalities. Immunotherapy is a particularly interesting alternative since it can potentially
affect metastatic disease.
PMID: 7927996 [PubMed - indexed for MEDLINE]
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