Ifosfamide Cisplatin

Glisson B, Scott C, Komaki R, et al. Cisplatin, Ifosfamide, prolonged oral etoposide and concurrent accelerated hyperfractionated thoracic radiotherapy for patients with limited small-cell lung cancer results of RTOG 93-12 (abstract 1733). Proc Am Soc Clin Oncol 1998 17 450a. 

Marked increments in response were observed with the incorporation of cisplatin into combination regimens response rates greater that 50% were reported in Phase-Ill studies of cisplatin/ifosfamide, cisplatin/ifosfamide/ bleomycin, and cisplatin/5-FU [188-190]. Randomized trials of these combinations administered prior to radiotherapy in locally advanced disease have not shown a survival advantage however, a recent GOG trial of concurrent cisplatin or cisplatin/5-FU/hydroxyurea and radiation was associated with significantly improved progression-free survival versus concurrent hydroxyurea and radiation in patients with Stage IIB-IVA cervical cancers [191]. Combined cisplatin and paclitaxel produced responses in 9 of 11 patients in a recent GOG study [192] and will be the focus of larger trials in the future. 

CISPLATIN IFOSFAMIDE t risk of neurotoxicity, haematotoxicity and tubular nephrotoxicity of ifosfamide due to t plasma concentrations of ifosfamide Cisplatin tends to cause renal damage, which results in impaired clearance of ifosfamide Do renal function tests before initiating therapy and during concurrent therapy, and adjust the dosage based on creatinine clearance values. Advise patients to drink plenty of water -vigorous hydration - and consider mesna therapy for renal protection... 

Hartmann JT, Fels LM, Franzke A, Knop S, Renn M, Maess B, Panagiotou P, Lampe H, Kanz L, Stolte H, Bokemeyer C. Comparative study of the acute nephrotoxicity from standard dose cisplatin + - ifosfamide and high-... 

Hartmarm JT, Fels LM, Knop S, Stolt H, Kattz L, Bokemeyer C. A randomized trial comparing the nephrotoxicity of cisplatin/ifosfamide-based combination chemotherapy with or without amifostine in patients with solid tumors. Invest New Drugs 2000 18(3) 281-9. 

Hartmann JT, Knop S, Fels LM, van Vangerow A, Stolte H, Kanz L, Bokemeyer C. The use of reduced doses of amifostine to ameliorate nephrotoxicity of cisplatin/ifosfamide-based chemotherapy in patients with solid tumors. Anticancer Drugs 2000 ll(l) l-6. 

Major risk factors for renal toxicity in cancer patients include nephrotoxic chemotherapy drugs, age, nutritional status, concurrent use of other nephrotoxic drugs (e.g., aminoglycoside antibiotics), and preexisting renal dysfunction. Drugs with a high risk for renal toxicity include cisplatin, ifosfamide,... 

The manufacturer of conventional amphotericin B states that nephrotoxic antineoplastics should not be given concurrently except with great caution. Of the antineoplastics, cisplatin, ifosfamide and methotrexate are well known for their nephrotoxicity. Amphotericin also reduces the renal clearance of methotrexate , (p.642). 

The renal toxicity of ifosfamide may be greater when used with cisplatin or in those who have had prior treatment with cisplatin. Ifosfamide may increase the hearing loss due to cisplatin. 

Salvage regimens incorporate drugs not used as initial therapy. Commonly used regimens include DHAP r/examethasone, Mgh-dose cytarabine, and cisplatin), ESHAP (etoposide, methylprednisolone, Mgh-dose cytarabine, and cisplatin), and MINE (mesna, ifosfamide, mitoxantrone, and etoposide). None is clearly superior to the others. 

ICE (ifosfamide, carboplatin, and etoposide) appears to be better tolerated than cisplatin-containing regimens, especially in elderly adults. 

IEP = ifosfamide, etoposide, cisplatin PEP = cisplatin, etoposide, paclitaxel EP = etoposide + cisplatin TP = topotecan+ paclitaxel E Carbo = etoposide + carboplatin. 

B = bleomycin, C = chlorambucil, CT = chemotherapy, DFS = disease-free survival, Ep = epirubicin, F = fluorouracil, I = ifosfamide, M = mitomycin C, Mtx = methotrexate, O = vincristine, OS = overall survival, P = cisplatin, RT = radiation therapy, V = vinblastine. 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

Metastatic osteosarcoma has a poor prognosis unless the disease is confined to the lungs and is resectable. Palliative chemotherapy can be employed with a number of drugs including doxorubicin, cisplatin, carboplatin, methotrexate, ifosfamide and etoposide. 

VIP Vincristine, ifosfamide, cisplatin (Platinol) Germ cell tumors... 

Carcinoma of testis Combination chemotherapy cisplatin, bleomycin, and etoposide Methotrexate, dactinomycin, plicamycin, vinblastine, doxorubicin, cyclophosphamide, etoposide, ifosfamide plus mesna1... 

Cervicai Cisplatin cyclophosphamide Bleomycin + ifosfamide + dsplacin... 

Endometrial Ewing s sarcomao" Gastric Head and neck,squamous cell Islet cell (pancreas) Kaposi s sarcoma Doxorubicin cisplatin + cyclophosphamide CAV Cyclophosphamide (or Ifosfamide) + doxorubicin (Adriamycin) + vincristine CF epirubidri + cisplatin 5-fluorouraci1 Cisplatin + S-fluorouracil Methotrexate Screptozotocin + S-fluorouracil Etoposide or interferon affa or vinblastine ABV doxorubicin (Adriamycin) + bteomycin + vincristine or vinblastine... 

Lung non-small cell) MIC mitomycin + ifosfamide cisplatin MVPi micomycin + vinblastine + cisplatin Cisplatin + gemcitabine vinorelbine... 

Ifosfamide is an alkylating agent belonging to the group of oxazaphosphorines. It is used to treat a variety of solid tumors in children, including rhabdomyosarcoma, soft tissue sarcomas, Wilms tumor, bone sarcomas, and neuroblastoma, and leukemias and lymphomas in adults. It is also sometimes used in combination with other drugs, such as doxorubicin or cisplatin and etoposide. 

Ifosfamide is associated with a peripheral neuropathy when it is given in combination with cisplatin (17). These symptoms improved within a few days after treatment with haloperidol. 

In several studies, intravenous amifostine (910 mg/m ) preserved glomerular filtration rate when it was co-administered with cisplatin-containing regimens (213). Even after two cycles containing intravenous cisplatin 50 mg/m plus intravenous ifosfamide and etoposide or paclitaxel, glomerular filtration rate can fall by more than 30%, but concomitant use of amifostine prevented this. Even lower dosages of intravenous amifostine (for example 740 mg/m ) may be effective (220,221). 

Pratt CB, Goren MP, Meyer WH, Singh B, Dodge RK. Ifosfamide neurotoxicity is related to previous cisplatin treatment for pediatric sohd tumors. J Clin Oncol 1990 8(8) 1399 01. 

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