Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy.
Adult ; Aged ; Antibiotics, Antineoplastic/adverse effects/therapeutic use ; Antimetabolites, Antineoplastic/adverse effects/therapeutic use ; Antineoplastic Agents/*adverse effects/therapeutic use ; Antineoplastic Agents, Alkylating/adverse effects/therapeutic use ; Drug-Induced Liver Injury/etiology/radiography ; Enzyme Inhibitors/adverse effects/therapeutic use ; Fatty Liver/etiology/radiography ; Female ; Humans ; Immunotherapy ; Liver Cirrhosis/etiology/radiography ; Liver Diseases/etiology/*radiography ; Male ; Middle Aged ; Neoplasms/therapy ; Tomography, X-Ray Computed

Antineoplastic Agents, Alkylating ; adverse effects ; therapeutic use ; Brain Neoplasms ; drug therapy ; Dacarbazine ; adverse effects ; analogs & derivatives ; therapeutic use ; Female ; Glioblastoma ; drug therapy ; Humans ; Leukemia, Myeloid, Acute ; chemically induced ; Middle Aged

OBJECTIVENimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas.

METHODSThe patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred. Individualized chemotherapy was administered based on O(6)-methylguanine-DNA methyltransferase (MGMT) expression and previous chemotherapy responses in combined with nimotuzumab.

RESULTSFourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 (median 7.5 times). Combined chemotherapy regimens included: continuous 21-day temozolomide (10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin (1 case), and teniposide plus nimustine (1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively. Disease control rate (PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI: 0.7 - 7.3) and PFS at 6 months was 30.6%. The most common toxicities include grade I-II neutropenia (2 cases), thrombocytopenia (2 cases), lymphopenia (1 case), nausea and vomitting (3 case) and asymptomatic transaminase increase (1 case). One patient developed grade IV neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash.

CONCLUSIONSNimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.

Adolescent ; Adult ; Antibodies, Monoclonal, Humanized ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Agents, Alkylating ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Astrocytoma ; drug therapy ; Child ; Cisplatin ; administration & dosage ; adverse effects ; Dacarbazine ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Glioblastoma ; drug therapy ; Glioma ; drug therapy ; Humans ; Infusions, Intravenous ; Male ; Nausea ; chemically induced ; Neutropenia ; chemically induced ; Nimustine ; administration & dosage ; adverse effects ; Teniposide ; administration & dosage ; adverse effects ; Thrombocytopenia ; chemically induced ; Young Adult

OBJECTIVETo observe the influences of FVP1 on both curative and negative effects of CTX.

METHODThe present study included two parts of experiments. In the part 1, 0.2 mL of 1 x 10(7) mL(-1) of S180 cells were inoculated in the subcutaneous layer of the right armpit of mice. All the mice were randomly divided into 3 groups: control group, in which mice were given with normal saline in 10 consecutive days, CTX group, in which mice were injected with 30 mg of CTX in the first and third days and saline in the other 8 days during the 10 consecutive days of treatment, and FVP1 and CTX group, in which the mice were injected with 30 mg x kg(-1) of CTX in the first and third days and FVP1 at 10 mg x kg(-1) in all 10 consecutive days of treatment. After above 10-day treatment , all the mice were killed and the tumor body was taken out and weighed to calculate the inhibiting rates on tumor. In the part 2 of experiments all the mice were divided into 3 groups: Normal control group, in which mice were not treated with any drugs, CTX-induced model group of inhibiting immune system, in which mice were injected with CTX at dose of 10 mg x kg(-1) in first two days and saline in the following 7 days; and small-, meddle-and large-dosage of FVP1 groups, in which mice were injected with CTX at the same dose as above in first two days and FVP1 intraperitoneally at 5, 10 and 20 mg x kg(-1) respectively in the following 7 days. CTX group was regarded as the control model. After the treatment, the peripheral white cells, thymus index, spleen index, the phagocytic power of macrophage of abdominal cavity, lymphocyte trastation rate and the activity of NK cell were detected.

RESULT(DFVP1 plus small dose of CTX obviously enhanced the inhibiting rate of CTX on tumor in the mice inoculated with S180 cells. (2) FVP1 at the different dose obviously antagozized CTX-induced leucopenia, atrophy, reduction of the phagocytic power of macrophage in abdominal cavity and restored the function of lymphocyte translation and the activity of NK cells.

CONCLUSIONFPV1 could enhance the curative effect of CTX in depressing tumor and attenuate the negative effect of CTX in inhibiting the function of immune system.

Agaricales ; chemistry ; Animals ; Antineoplastic Agents, Alkylating ; adverse effects ; pharmacology ; Cell Line, Tumor ; Cyclophosphamide ; adverse effects ; pharmacology ; Dose-Response Relationship, Drug ; Drug Synergism ; Killer Cells, Natural ; drug effects ; Leukopenia ; chemically induced ; Lymphocyte Activation ; drug effects ; Macrophages, Peritoneal ; physiology ; Mice ; Neoplasm Transplantation ; Phagocytosis ; drug effects ; Polysaccharides ; isolation & purification ; pharmacology ; Random Allocation ; Sarcoma 180 ; pathology

Ifosfamide-induced Fanconi syndrome is a rare complication that typically occurs in young patients due to a cumulative dose of ifosfamide > 40-60 g/m2, a reduction in kidney mass, or concurrent cisplatin treatment. It is usually characterized by severe and fatal progression accompanied by type II proximal renal tubular dysfunction, as evidenced by glycosuria, proteinuria, electrolyte loss, and metabolic acidosis. Diabetes insipidus is also a rare complication of ifosfamide-induced renal disease. We herein describe a case involving a 61-year-old man who developed ifosfamide-induced Fanconi syndrome accompanied by diabetes insipidus only a few days after the first round of chemotherapy. He had no known risk factors. In addition, we briefly review the mechanisms and possible therapeutic options for this condition based on other cases in the literature. Patients who receive ifosfamide must be closely monitored for renal impairment to avoid this rare but fatal complication.
Acidosis/chemically induced ; Antineoplastic Agents, Alkylating/*adverse effects ; Chemotherapy, Adjuvant ; Diabetes Insipidus/*chemically induced/diagnosis/therapy ; Fanconi Syndrome/*chemically induced/diagnosis/therapy ; Fatal Outcome ; Histiocytoma, Malignant Fibrous/*drug therapy/pathology ; Humans ; Ifosfamide/*adverse effects ; Male ; Middle Aged ; Neoadjuvant Therapy/*adverse effects ; Time Factors

OBJECTIVETo study the safety and efficacy of three-dimensional conformal radiotherapy in combination with temozolomide in treatment of patients with diffuse brainstem glioma.

METHODSTwelve patients with MRI-confirmed diffuse brainstem glioma received 54 Gy three-dimensional conformal radiotherapy for 6 weeks with 1.8 Gy per fraction, 5 times per week. All of the patients were given daily oral temozolomide 75 mg/m(2) during radiotherapy. Four weeks after radiotherapy, all of the patients received 6 cycles of temozolomide, each cycle lasted 5 days with 28 days interval between each two cycles. 150 mg/m(2) of temozolomide was given for the first cycle for five days, followed by 200 mg/m(2) of the drug for the rest of the cycles if no significant drug-related toxicities were observed. Magnetic resonance imaging and laboratory tests were performed to evaluate the efficacy and adverse reactions.

RESULTSIn the 12 patients, CR was 1 case (8.3%), PR 6 cases (50.0%), SD 2 cases (16.7%), and PD 3 cases (25.0%). The overall clinical benefit rate was 75.0%. Progression-free survival rate was 75.0% (9/12) at 6 months and 50.0% (6/12) at 1 year. The one-year overall survival rate was 75.0%. There were no severe temozolomide-related toxicities.

CONCLUSIONSConcurrent temozolomide with three-dimensional conformal radiotherapy and followed by 6 cycles of temozolomide chemotherapy for diffuse brainstem gliomas have a better clinical efficacy, good tolerance and with no severe toxicities.

Adolescent ; Adult ; Antineoplastic Agents, Alkylating ; adverse effects ; therapeutic use ; Brain Injuries ; etiology ; Brain Stem Neoplasms ; pathology ; therapy ; Chemoradiotherapy ; Child ; Dacarbazine ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Female ; Glioma ; pathology ; therapy ; Humans ; Leukopenia ; chemically induced ; Male ; Middle Aged ; Radiation Injuries ; etiology ; Radiotherapy, Conformal ; adverse effects ; methods ; Remission Induction ; Survival Rate ; Young Adult

The purpose of this study was to develop a cost-effective protocol for the mobilization of peripheral blood stem cells (PBSC) in patients with malignancy. Thirty consecutive patients were randomized to mobilize PBSC with the late addition of a standard 250 microg dose of G-CSF (Neutrogen) from day 8 or early addition of the same dose of G-CSF from day 2, following cyclophosphamide (CY) 4 g/m2. The median yield of CD34+ cells from evaluated patients was 7.87 x 10(6)/kg (range, 2.06-27.25), collected in a median of four apheresis (range, 2-9). Target CD34 + cell doses > or = 2.0 x 10(6)/kg were achieved in all patients able to be evaluated. There were no statistically significant differences in CD34+ cell yields or toxicities. Overall engraftment occurred with median days to neutrophils > or = 0.5 x 10(9)/L or platelets > 20 x 10(9)/L of 11 and 17 days, respectively. However, the duration of G-CSF administration was markedly shorter in the late use of G-CSF group than in the early use of G-CSF group, with a median of 9 days compared with 15 days (p>0.001). PBSC harvesting after priming with CY plus delayed use of G-CSF made it a safe and cost-effective procedure.
Adult ; Aged ; Antigens, CD34/metabolism ; Antigens, CD34/immunology ; Antineoplastic Agents, Alkylating/therapeutic use* ; Antineoplastic Agents, Alkylating/adverse effects ; Breast Neoplasms/therapy ; Comparative Study ; Cost-Benefit Analysis ; Cyclophosphamide/therapeutic use* ; Cyclophosphamide/adverse effects ; Drug Administration Schedule ; Female ; Graft Survival ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Granulocyte Colony-Stimulating Factor/adverse effects ; Hematopoietic Stem Cell Mobilization/methods* ; Hematopoietic Stem Cell Mobilization/economics* ; Hematopoietic Stem Cell Mobilization/adverse effects ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/metabolism ; Hematopoietic Stem Cells/immunology ; Human ; Lymphoma, Non-Hodgkin/therapy ; Male ; Middle Age ; Multiple Myeloma/therapy ; Sarcoma, Ewing's/therapy

Combination chemotherapy and radiation therapy have contributed to the successful treatment of various cancer patients. But the development of second malignancies is an inevitable complication of long-term cytotoxic treatment. The most serious and frequent of such complications is acute myelogenous leukemia (AML). Therapy-related leukemia is generally fatal. Since the number of patients exposed to chemotherapy is increasing each year, the clinical significance of this entity cannot be underestimated. There have been many investigations of therapy-related leukemia, but in Korea published reports are rare. We describe four such cases, involving one older female with lung cancer and three children with acute lymphoblastic leukemia (ALL) and malignant lymphoma. Alkylating agents were used for chemotherapy, and in one case, topoisomerase II inhibitor. Irrespective of the causative agents, the latency periods were relatively short, and despite induction chemotherapy in two, all survived for only a few months. During the follow-up of patients treated for primary malignancies, the possibility of therapy-related leukemia should always be borne in mind.
Adolescence ; Aged ; Antineoplastic Agents, Alkylating/therapeutic use* ; Antineoplastic Agents, Alkylating/adverse effects ; Carcinoma, Small Cell/radiotherapy ; Carcinoma, Small Cell/drug therapy ; Case Report ; Child ; DNA Topoisomerase (ATP-Hydrolysing)/antagonists & inhibitors ; Fatal Outcome ; Female ; Human ; Leukemia, Lymphocytic, Acute, L1/drug therapy ; Leukemia, Monocytic, Acute/etiology ; Leukemia, Myelocytic, Acute/etiology* ; Leukemia, Myelomonocytic, Acute/etiology* ; Lung Neoplasms/radiotherapy ; Lung Neoplasms/drug therapy ; Lymphoma, B-Cell/radiotherapy ; Lymphoma, B-Cell/drug therapy ; Male ; Neoplasms, Second Primary/etiology*

This study evaluated the toxicity profiles of temozolomide in the treatment of malignant glioma as either concurrent or adjuvant chemotherapy. We retrospectively reviewed the medical records of 300 malignant glioma patients treated with temozolomide in two medical institutions in Korea between 2004 and 2010. Two hundred nine patients experienced a total of 618 toxicities during temozolomide therapy. A total of 84.8% of the 618 toxicities were Common Terminology Criteria for Adverse Events (CTCAE) grade 1 or 2, while 15.2% were grade 3 or 4. Among the hematologic toxicities, thrombocytopenia (13.7%), anemia (11.0%), and AST/ALT increases (7.0%) were common. Among the non-hematologic toxicities, nausea (44.3%), vomiting (37.0%), and anorexia (14.3%) were the three most common toxicities. There was no mortality due to temozolomide. Although temozolomide showed many types of toxicities, the majority of the toxicities were tolerable and of lower grade. Gastrointestinal troubles are the most common toxicities in Korean patients treated with temozolomide.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anorexia/etiology ; Antineoplastic Agents, Alkylating/adverse effects/*therapeutic use ; Brain Neoplasms/*drug therapy/pathology/radiotherapy ; Dacarbazine/adverse effects/*analogs & derivatives/therapeutic use/toxicity ; Female ; Glioma/*drug therapy/pathology/radiotherapy ; Hematologic Diseases/etiology ; Humans ; Male ; Middle Aged ; Nausea/drug therapy/etiology ; Neoplasm Staging ; Republic of Korea ; Retrospective Studies ; Severity of Illness Index ; Sex Factors ; Vomiting/drug therapy/etiology ; Young Adult

Temozolomide is an oral alkylating agent with clinical activity against glioblastoma multiforme (GM). It is generally well-tolerated and has few pulmonary side effects. We report a case of temozolomide-associated brochiolitis obliterans organizing pneumonia (BOOP) requiring very high-dose corticosteroid treatment. A 56-yr-old woman presented with a 2-week history of exertional dyspnea. For the treatment of GM diagnosed 4 months previously, she had undergone surgery followed by chemoradiotherapy, and then planned adjuvant chemotherapy with temozolomide. After the 1st cycle, progressive dyspnea was gradually developed. Chest radiograph showed diffuse patchy peribronchovascular ground-glass opacities in both lungs. Conventional dose of methylprednisolone (1 mg/kg/day) was begun for the possibility of BOOP. Although transbronchial lung biopsy findings were compatible with BOOP, the patient's clinical course was more aggravated until hospital day 5. After the dose of methylprednisolone was increased (500 mg/day for 5 days) radiologic findings were improved dramatically.
Antineoplastic Agents, Alkylating/*adverse effects/therapeutic use ; Cryptogenic Organizing Pneumonia/*chemically induced/*drug therapy/radiography ; Dacarbazine/adverse effects/*analogs & derivatives/therapeutic use ; Dyspnea/etiology ; Female ; Glioblastoma/drug therapy/radiography ; Glucocorticoids/*therapeutic use ; Humans ; Methylprednisolone/therapeutic use ; Middle Aged ; Tomography, X-Ray Computed