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At least 1,207 records · Page 67Linked to original sources
PubMed2006

Concomitant administration of vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide for high-risk sarcomas: the St. Jude Children's Research Hospital experience.

BACKGROUND: Intensified chemotherapy may improve the outcome of patients with high-risk pediatric sarcomas. Vincristine, doxorubicin, cyclophosphamide, ifosfamide, and etoposide are highly effective against pediatric sarcomas. The authors investigated the feasibility of administering these agents concomitantly within a defined period. METHODS: In the prospective high-risk sarcoma (HIRISA) Phase II trial HIRISA1, pediatric patients with high-risk sarcomas received 3 cycles of intensive vincristine, ifosfamide, etoposide, cyclophosphamide, and doxorubicin (VACIE) before radiotherapy and/or surgery began at Week 9 with concurrent vincristine, cyclophosphamide, and doxorubicin (Week 9) and vincristine and ifosfamide (Week 12). Three additional cycles of VACIE were then given. After delayed hematologic recovery in the first 11 patients, the protocol was modified (HIRISA2) to delay local control therapy until after 5 cycles of VACIE (to be completed within 18 weeks). Patients who responded to the protocols were eligible for myeloablative consolidation with autologous stem cell support. RESULTS: Eleven of 24 patients (median age, 14.9 years) had Ewing sarcoma family of tumors, 9 patients had rhabdomyosarcoma, and 4 patients had unresectable desmoplastic small round cell tumors. Seven of 13 patients on HIRISA2, but none of 11 patients on HIRISA1, completed therapy within the specified time. Reversible Grade 4 myelosuppression was the most common toxicity. Major nonhematologic toxic effects were mucositis, nutritional impairment, hypotension, and peripheral neuropathy. Three patients died of toxicity. The 5-year survival and 5-year event-free survival estimates both were 45.8% +/- 11.2%. CONCLUSIONS: The feasibility of administering intensive chemotherapy regimens like VACIE was dependent in part on the timing of local control therapy. This regimen was associated with significant toxicity.

Adolescent↗
PubMed1983

The kinetics of in vivo sister chromatid exchange induction in mouse bone marrow cells by alkylating agents: cyclophosphamide.

Administration of cyclophosphamide (5, 10, 20 and 25 mg/kg body weight) to male CD-1 mice 2 hr after subcutaneous implantation of a 5-bromo-2'-deoxyuridine (BrdUrd) pellet (55 mg) resulted in a dose-dependent increase in sister chromatid exchanges (SCE) in bone marrow cells. Treatment with cyclophosphamide (15 mg/kg body weight) at the time of BrdUrd implantation and 2, 6.5, and 13 hr post-BrdUrd implantation resulted in the induction of approximately 19 SCE/cell indicating that the bone marrow SCE response was independent of the time of administration. Treatment with cyclophosphamide (15 mg/kg body weight) at 26, 19, 13, and 6 hr prior to BrdUrd implantation resulted in baseline SCE (3.3 SCE/cell) at 26 hr with an increasing number of SCE/cell with decreasing time prior to BrdUrd implantation. These results compare favorably with those obtained by Kram et al [1981] with mitomycin C (MMC) using a similar protocol. The time-dependent induction of SCE is qualitatively similar for CP and MMC, both of which are bifunctional alkylating agents metabolically activated by oxidation and reduction, respectively, and suggests that these two compounds may induce SCE by a similar mechanism.

Animals↗
PubMed1995

Cyclophosphamide plus tumor necrosis factor-alpha chemoimmunotherapy cured mice: life-long immunity and rejection of re-implanted primary lymphoma.

Changes in functionally and phenotypically definable splenocyte subsets in aging mice which had been rendered tumor-free in early life by immunochemotherapy (cyclophosphamide plus tumor necrosis factor-alpha) were studied in the syngeneic EL4 lymphoma-C57BL/6 murine model. Treatment-induced long-term survivors (LTS) surviving rechallenge are termed "immune-LTS". On day 120 (day 0, initial tumor inoculation), splenocytes from day 60 rechallenged immune-LTS developed significantly greater specific anti-EL4 cytolytic activity in an ex vitro assay than those from non-rechallenged LTS. Splenocytes from combination-treated groups developed significantly higher activity than those from cyclophosphamide-induced immune-LTS. The splenic effector precursor was a CD8+ T cell. The specific anti-EL4 effector cell from the cyclophosphamide-induced immune-LTS was CD4- CD8+; however, approximately 50% of those from combination-treated immune-LTS appeared to be CD4+CD8+. On day 520 immune-LTS were randomized into 2 groups. One group was re-implanted with EL4 tumor; all mice survived. The other group was killed and, even though their splenocytes developed considerable anti-EL4 activity, their allogeneic responsiveness was as reduced as that of age-matched controls. Phenotypic analysis, compared with splenocytes from young and age-matched controls, revealed changes in the makeup of each T-cell subset, except the CD4+CD8+, and all subsets, except the CD4-CD8-, had increases in CD44 positivity. On day 625, the age of these mice was equivalent to the median life-span of C57BL/6 mice; nevertheless, their splenocytes developed high anti-EL4 activity. Phenotypic analysis indicated that, compared to day 520, there was a major decrease in CD4-CD8+ splenocytes; we suggest that these cells had migrated to the site of tumor eradication.

Animals↗
PubMed1985

Cyclophosphamide-related intravascular haemolysis during continuous-flow plasma exchange.

The plasma of a patient being prepared for allogeneic bone marrow transplantation was found to be severely lymphocytotoxic to donor cells. Three isovolaemic plasma exchanges carried out using a continuous-flow technique were required to reduce this titre to undetectable levels. Neither these procedures nor pretransplantation conditioning of the patient with 60 mg/kg or cyclophosphamide on two consecutive days resulted in overt haemolysis. However, a single identical plasmapheresis 12 hours after completing the second dose of the alkylating agent resulted in profound intravascular haemolysis requiring red cell transfusion. Subsequent studies in five patients receiving the same cyclophosphamide regimen demonstrated that red cell life span, when measured with radiochromium, was reduced from a normal of 25-35 days to a median of 11.5 days. Further studies in the same five patients carried out simultaneously demonstrated that red cell fragility, when assessed in vitro with osmotic or mechanical stress, was marginally increased but became clearly abnormal in only one individual. These doses of cyclophosphamide may result in accelerated but subclinical red cell destruction, and plasma exchange in this period may be associated with rapid intravascular haemolysis. This complication should now be added to the list of those that can occur when plasmapheresis is required in this specific clinical situation.

Adult↗
PubMed1981

The spread and persistence of influenza viruses in normal and cyclophosphamide-treated mice.

The persistence and extrapulmonary spread of three strains of influenza virus, the mouse neuro-adapted A/NWS virus, the wild-type strain A/Victoria/75, and a recombinant virus RIT4050, bearing surface antigens derived from A/Victoria/75, were studied in both normal and cyclophosphamide-treated CBA mice following either intranasal or intracerebral inoculation. All three viruses showed increased lethality in mice in the presence of cyclophosphamide but exhibited distinctive patterns of replication and spread. The recombinant virus RIT4050 showed a reduced ability to replicate, persist, and spread in CBA mice compared to either A/NWS or A/Victoria/75 viruses, and in general, the A/NWS virus persisted to a greater extent than the A/Victoria/75 virus in both normal and treated mice. However, in the presence of cyclophosphamide, no extrapulmonary spread of A/NWS virus was observed. The reasons for the differences are discussed.

Administration, Intranasal↗
PubMed1978

Response of intramuscular Walker 256 rat tumor to sustained-release cyclophosphamide and ARA-C capsules.

Randomly bred Sprague-Dawley rats with the intramuscular form of Walker 256 tumor growing in the right thigh region were treated with sustained-release cyclophosphamide capsules as well as with cytosine arabinoside capsules. A disk-shaped caps-le was implanted subcutaneously adjacent to the tumor mass. Tumor regression, weight gain, and prolongation of lifespan were observed in animals treated with cyclophosphamide capsules of 10 mg or 20 mg total drug content each. However, the walker 256 intramuscular tumor did not respond to ARA-C capsules implanted, and the animals died at the same rate as the controls, with large ulcerated tumor masses and some metastasis. The in vitro diffusion data of ARA-C capsules is shown. Gross and histological changes associated with cyclophosphamide administered in this manner are reported.

Animals↗
PubMed1975

The effect of short-term cyclophosphamide on estrogen therapy in metastatic breast cancer.

Stimulation of tumor growth and induced hypercalcemia both may occur during the initiation of estrogen therapy in breast cancer. This study was conducted to determine whether cyclophosphamide (CTX) as an adjuvant to estrogen therapy might (1) prevent induced hypercalcemia or (2) achieve a higher tumoricidal effect during the phase of tumor stimulation. Fifty postmenopausal women with inoperable or recurrent disseminated breast carcinoma were divided into two random groups. Results could be evaluated in 44 patients; 21 received diethylstilbestrol (DES), and 23 received DES plus a 4-week course of cyclophosphamide (DES + CTX). The response rate was 5/21 (24%) in the DES group and 8/23 (35%) in the DES + CTX group (p greater than 0.05). The median duration of response for both groups was 9 months. The survival rate at 24 months was 52% in the DES group and 25% in the DES + CTX group (p = 0.05). Induced hypercalcemia occurred in 3 patients treated with DES + CTX. Short-term cyclophosphamide adjuvant to estrogen therapy did not prevent induced hypercalcemia nor prolong the duration of response or survival.

Age Factors↗
PubMed1982

Chronic idiopathic thrombocytopenic purpura (ITP:) development of acute non-lymphocytic leukemia subsequent to treatment with cyclophosphamide.

Chronic idiopathic thrombocytopenic purpura (ITP) is most often treated successfully with steroids and/or splenectomy. In those who fail to respond with the foregoing treatment, immunosuppressive drugs are sometimes added to the regimen. Cyclophosphamide has been reported heretofore to be effective with a minimum of side effects and complications. However, the use of alkylating agents and the induction of a second malignancy is now well recognized. This report describes three cases of refractory ITP treated with cyclophosphamide who subsequently developed an acute non-lymphocytic leukemia. Cyclophosphamide should be used with discretion in the treatment of chronic idiopathic thrombocytopenic purpura which is a non-neoplastic disorder.

Adult↗
PubMed1995

Dose escalation trial of cyclophosphamide with Sargramostim in the treatment of central nervous system (CNS) neoplasms.

We conducted a dose escalation trial of cyclophosphamide plus Sargramostim in the therapy of patients with newly diagnosed or recurrent central nervous system tumors. Cyclophosphamide was administered at doses ranging between 1.0 and 2.5 g/m2 daily for two doses. Sargramostim was administered at a fixed dose of 250 micrograms/m2 subcutaneously twice a day beginning 24 hours after the second cyclophosphamide dose and continuing through the leukocyte nadir until the absolute neutrophil count (ANC) was > 1,000 cells/microliters for two consecutive days. The MTD for patients who had not received any prior chemotherapy and who had received either no radiotherapy or radiotherapy confined to the cranium was 2.0 g/m2 daily for two doses. The MTD for patients previously treated with chemotherapy or neuraxis radiotherapy was also 2.0 g/m2 daily for two doses. Responses were seen in patients with medulloblastoma (8/9), glioblastoma multiforme (2/13), germinoma (1/1), and pineoblastoma (1/2).

Adolescent↗
PubMed1982

Treatment of ongoing experimental myasthenia gravis with short term high dose cyclophosphamide.

We have treated animals with an ongoing autoimmune disease, experimental autoimmune myasthenia gravis (EAMG), using a strategy designed to eliminate the antibody-producing cells. During well-established EAMG, a single high dose of cyclophosphamide was given because of its known effectiveness against B-lymphocytes. To counteract the lethal effects of the drug, the rats were "rescued" by bone marrow cell transplantation. This treatment produced a rapid and sustained fall of antibody titers against both the immunizing antigen (Torpedo acetylcholine receptor) and the autoantigen (rat acetylcholine receptor). Immunologic memory, as measured by an anamnestic response to the antigen, was partially suppressed. Cyclophosphamide treatment produced improvement in the neuromuscular defect: treated animals had, on the average, twice as many acetylcholine receptors at neuromuscular junctions compared with untreated EAMG animals. This treatment method of short-term high doses of an immunosuppressive drug, such as cyclophosphamide, may eventually prove useful for human myasthenia gravis and other autoimmune diseases.

Animals↗
PubMed2004

Intensive cisplatin and cyclophosphamide-based chemotherapy without radiotherapy for intracranial germinomas: failure of a primary chemotherapy approach.

PURPOSE: High rates of overall and event-free survival have been reported in patients with intracranial germinomas treated with craniospinal radiotherapy. More recently, similar results have been reported with chemotherapy combined with radiotherapy to more localized treatment volumes. Our interest in exploring chemotherapy without radiotherapy in patients with CNS germinomas was based on concerns about the late sequelae of radiotherapy to the brain or neuraxis and also the well documented success of chemotherapy alone in patients with disseminated extracranial germinomas. The primary objective of this study was to determine whether intensive cisplatin and cyclophosphamide-based combination chemotherapy, without radiotherapy, was effective in patients with CNS germinomas. PATIENTS AND METHODS: Nineteen patients were enrolled, ranging in age from 1 to 24 years (median, 14 years). Thirteen were male. Nine had diabetes insipidus. Therapy comprised two courses of Regimen 'A' (cisplatin, etoposide, cyclophosphamide, and bleomycin) followed by MRI evaluation. Patients achieving a complete remission (CR) completed all planned therapy with two courses of regimen 'B' (carboplatin, etoposide, and bleomycin). Patients achieving less than a CR received two courses of Regimen 'B' followed by another evaluation. Those in CR after four courses of treatment received one additional course of Regimen 'A' and Regimen 'B', while those not in CR after four treatment courses underwent second look surgery and/or radiation therapy. RESULTS: Eleven of 11 patients with residual postoperative disease assessable for response achieved a CR. With a median follow-up of 6.5 years, eight out of 19 (0.42) patients remain in CR 1 without radiotherapy and another three patients are in stable second or subsequent remissions. Three patients died from treatment-related toxicity and another died in CR 1 from an uncharacterized leukoencephalopathy. The 5-year event-free survival (EFS) was 0.47 +/- 0.23 and 5-year overall survival (OS) was 0.68 +/- 0.22. CONCLUSIONS: Intensive cisplatin and cyclophosphamide-based chemotherapy was effective in achieving remissions, however, the long-term outcome using this treatment program was unsatisfactory and associated with unacceptable morbidity and mortality, particularly in patients with diabetes insipidus.

Adolescent↗
PubMed2007

A phase II trial of thalidomide and cyclophosphamide in patients with recurrent or refractory pediatric malignancies.

BACKGROUND: Previous clinical and pre-clinical research has demonstrated synergy between anti-angiogenic agents and cytotoxic chemotherapy. This trial was undertaken to investigate whether the combination of cyclophosphamide and thalidomide would be active against pediatric tumors. PROCEDURE: Patients with pediatric malignancies who had no remaining conventional therapeutic options were recruited from January 1999 to May 2001. They received thalidomide (6-12 mg/kg po every day; maximum daily dose 800 mg) and cyclophosphamide (1,200 mg/m2 IV every 28 days). RESULTS: Twenty-seven patients were enrolled on the study. Seventeen were male and 10 were female. Median age at the time of registration was 15 years (range 1-54 years). The median number of prior treatment regimens was four. Twenty-one patients were evaluable for response; 1 had a partial response (Hodgkin disease), 1 demonstrated stable disease (neuroendocrine tumor), and 19 had progressive disease. The most common toxicities were hematological (leukocytopenia and neutropenia) and gastrointestinal. One patient experienced a grade 3 rash. Fatigue and daytime somnolence were variable. No peripheral neuropathy was observed. CONCLUSION: The combination of thalidomide and cyclophosphamide as described herein has a modest and tolerable toxicity profile but little evidence of efficacy.

Adolescent↗
PubMed2005

Simultaneous quantification of fludarabine and cyclophosphamide in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry.

Fludarabine and cyclophosphamide are anticancer agents mainly used in the treatment of hematologic malignancies. We have developed and validated an assay using high-performance liquid chromatography (HPLC) coupled with electrospray ionization tandem mass spectrometry for the quantification of fludarabine in combination with cyclophosphamide in human heparin and human EDTA plasma. Sample pre-treatment consisted of a protein precipitation with cold acetonitrile (-20 degrees C) using 250 microL of plasma. Separation was performed on an Extend C18 column (150 x 2.1 mm i.d.; 5 microm) with a stepwise gradient using 1 mM ammonia solution and acetonitrile at a flow rate of 400 microL/min. The analytical run time was 12 min. The triple quadrupole mass spectrometer was operated in the positive ion mode and multiple reaction monitoring was used for drug quantification. The method was validated over a concentration range of 1 to 100 ng/mL for fludarabine and cyclophosphamide in human heparin and human EDTA plasma. The coefficients of variation were <13.9% for inter- and intra-day precisions. Mean accuracies were also within the designated limits (+/-15%). The analytes were stable in plasma, processed extracts and in stock solution under all relevant conditions.

Antineoplastic Agents↗
PubMed1986

An assessment of the effects of cyclophosphamide and sodium valproate on the viability of preimplantation mouse embryos using the fluorescein diacetate test.

The fluorescein diacetate test is a measure of both esterase enzyme activity and membrane integrity and it has been shown to be useful in assessing the viability of a variety of cells cultured in vitro, mouse embryos after freezing and thawing, and mouse embryos grown under inadequate culture conditions. In this study, the effects were examined of cyclophosphamide and sodium valproate administered respectively to pregnant inbred CBA mice 60 h after fertilization, on the viability of 84-h blastocysts. Cyclophosphamide 20 and 40 mg/kg bodyweight and sodium valproate 90 mg/kg significantly increased the number of nonviable blastocysts. Cyclophosphamide 4 mg/kg and sodium valproate 23 and 45 mg/kg did not adversely affect blastocyst viability. The intensity of embryo fluorescence correlated well with the subsequent development of the embryos in culture (r = 0.863; p less than 0.001). The test had a sensitivity of 83% and a specificity of 100%. Exposure of embryos to fluorescein diacetate under the conditions of this experiment did not adversely influence the subsequent postimplantation development of 84-h blastocysts cultured in vitro for a further 120 h. These findings suggest that the fluorescein diacetate test is a simple, rapid, and nontoxic procedure that may be useful in assessing the viability of preimplantation embryos after exposure to embryotoxic drugs and chemicals.

Animals↗
PubMed1980

The use of cultured rat embryos to evaluate the teratogenic activity of serum: cadmium and cyclophosphamide.

Head fold stage rat embryos were cultured for 48 hours in vitro on serum taken at various intervals from rats that had been injected ip with either cadmium or cyclophosphamide. Their response was compared to that of embryos cultured for the same period on control serum to which these substances were added directly. One and 4 hour sera from cadmium-injected rats (2.13 mgCd++/kg) were lethal. Eight hour serum allowed survival but embryos were exencephalic and contained reduced amounts of protein and DNA. The response to direct cadmium was characteristically different and was related to dosage and the extent to which zero-time embryos had progressed through the head fold stage. At 1.6 micro M, Cd++ susceptible embryos were hemorrhagic, though not exencephalic. One hour serum from rats given cyclophosphamide (180 mg/kg) was lethal. On 4 hour serum, embryos survived but were exencephalic and contained less protein and DNA than controls. Embryos were resistant to direct cyclophosphamide up to 800 micrograms per ml of medium. At this concentration, embryos appeared morphologically normal but contained reduced amounts of protein.

Animals↗
PubMed1989

Effects of phosphoramide mustard and acrolein, cytotoxic metabolites of cyclophosphamide, on mouse limb development in vitro.

Phosphoramide mustard and acrolein are toxic and reactive metabolites of the widely used anticancer drug and known teratogen cyclophosphamide. To study the mechanism(s) involved and to determine which of the active metabolites of cyclophosphamide is responsible for the production of limb malformations, the effects of exposure of cultured limb buds to phosphoramide mustard and acrolein were investigated. Fore- and hindlimbs were excised from ICR mice on day 12 of gestation and cultured in roller bottles for 6 days. Limbs were exposed to either phosphoramide mustard or acrolein (10 or 50 micrograms/ml) for the first 20 hours of the culture period. Exposure to phosphoramide mustard produced limb reduction malformations in both the fore- and hindlimbs; total limb bone area was greatly reduced, while the relative contribution of the paw to this area in forelimbs was increased. There was a fourfold reduction in both DNA and RNA; protein content was reduced only by one-half. Alkaline phosphatase activity was significantly decreased in fore- and hindlimbs exposed to phosphoramide mustard, whereas creatine phosphokinase activity was only reduced in hindlimbs in the limbs exposed to the higher concentration of phosphoramide mustard. Exposure to acrolein also produced malformed limbs with a mangled appearance; however, total limb bone area and the relative contribution of the long bones versus paw structures were not altered. Acrolein exposure had little effect on growth parameters such as DNA (decreased only in hindlimbs exposed to 50 micrograms/ml), RNA (increased in hindlimbs exposed to 50 micrograms/ml), or protein content. Alkaline phosphatase and creatine phosphokinase activities were not altered in acrolein-exposed fore- or hindlimbs. Thus, phosphoramide mustard and acrolein have dramatically different effects on developing limbs in vitro; this observation may indicate that they have different targets and/or mechanisms of action as teratogens in the limb. The effects of phosphoramide mustard are very similar to those of "activated" cyclophosphamide (4-hydroperoxycyclophosphamide).

Acrolein↗
PubMed1995

A phase I study of intraperitoneal interferon-alpha 2b and intravenous cis-platinum plus cyclophosphamide chemotherapy in patients with untreated stage III epithelial ovarian cancer: a Gynecologic Oncology Group pilot study.

Previous clinical investigations using interferons (IFNs) have shown activity against epithelial ovarian cancer. The objective of this study was to determine the maximum tolerated dose of intraperitoneal (ip) IFN-alpha 2b which could be administered in combination with intravenous (iv) cis-platinum plus cyclophosphamide chemotherapy. After comprehensive surgical staging and maximal cytoreduction, previously untreated patients with primary ovarian adenocarcinoma were entered at one of five IFN dose levels. IFN-alpha 2b (5-30 x 10(6) units) was administered ip on Day 1 (+/- Day 8). cis-Platinum (75 mg/m2) plus cyclophosphamide (750 mg/m2) were administered iv on Day 2 with prophylactic hydration and anti-emetics. Courses were repeated every 3 weeks for 8 cycles. Adverse effects were recorded using standard Gynecologic Oncology Group toxicity scales. Fifteen patients with mean age 56 years (range 43-73) were entered and received a combined total of 100 treatment cycles. Catheter-related complications occurred in 8 patients, and in three cases lead to catheter removal and discontinuation of ip therapy. Two patients experienced grade 2-3 nephrotoxicity and 1 experienced grade 2 peripheral neuropathy. There was a single episode of chemical peritonitis. Myelosuppression was the dose-limiting toxicity with grade 3-4 leukopenia complicating 6, 5, 12, 11, and 17 cycles at dose levels 1-5, respectively. No patient completed planned treatment without interruption or dose reduction. Planned cis-platinum dose intensity was most compromised at the fifth IFN-alpha 2b dose level. The maximum tolerated dose of IFN-alpha 2b was determined to be 20 x 10(6) units repeated on Days 1 and 8 of this 21-day cis-platinum plus cyclophosphamide chemotherapy cycle.

Adenocarcinoma↗
PubMed1996

A phase I/II study of dose-intense paclitaxel with cisplatin and cyclophosphamide as initial therapy of poor-prognosis advanced-stage epithelial ovarian cancer.

Epithelial ovarian cancer patients with bulky residual tumor have a poor response to therapy and limited survival. We investigated the addition of dose-intense paclitaxel to cisplatin and cyclophosphamide for patients with FIGO III/IV epithelial ovarian cancer. Paclitaxel dose was intensified from 135 to 250 mg/m2 and administered in combination with cisplatin at > or = 75 mg/m2 and cyclophosphamide at 750 mg/m2. Thirty-one of 36 patients (86%) and 25 (70%) had > or = 2 and > or = 3 cm residual disease after surgery, respectively. One-third had stage IV disease, and 80% had grade 3 tumors. The maximally tolerated doses (MTD) were paclitaxel at 250 mg/m2, cisplatin at 75 mg/m2, and cyclophosphamide at 750 mg/m2 on a 21-day cycle with G-CSF, 10 micrograms/kg/day. Administered dose intensity at the MTD was > or = 86%. Reversible grade 3 peripheral neuropathy occurred in 28% of patients and fever during neutropenia in 2/352 cycles (0.5%). The pathologic response rate is 36% with an additional 25% having minimal microscopic disease. Median progression-free and overall survivals for patients receiving paclitaxel at 250 mg/m2 at a median potential follow-up of 22 months have not been reached for the cohort nor for the > or = 3-cm subgroup. This regimen should be evaluated in a prospective, randomized clinical trial.

Adult↗