Cisplatin with methotrexate

Loehrer PJ, Einhom LH, Elson PJ, et al. A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma a cooperative group study. J Clin Oncol 1992 7 1066-1073. 

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. 

METHOTREXATE CISPLATIN t methotrexate levels, with t risk of pulmonaiy toxicity Cisplatin is the most common anticancer drug associated with renal proximal and distal tubular damage. Cisplatin could significantly l renal elimination of methotrexate It would be best to start with lower doses of methotrexate. It is necessary to assess renal function prior to and during concurrent treatment until stability is achieved. Monitor clinically and with pulmonary function tests... 

Anti-tumour therapy can have serious effects. Gonadal failure arising from radiotherapy or chemotherapy is frequently encountered. Hypomagnesaemia and hypokalaemia may be a consequence of the use of the cytotoxic drug, cisplatin. Patients treated with methotrexate may become folate deficient. 

Items 80-81. A patient with metastatic choriocarcinoma was ti eated first with methotrexate plus dactinomycin and subsequently with a combination of cisplatin and vincristine. In both regimens, drug dosage was maximized to a toxicity limit of a 2-log decrease in blood platelets. The effects of chemotherapy were monitored by urinary chorionic gonadotropin (UCG, U/24 h), as shown in the data below. 

Intravenous Chemotherapy. The most effective chemotherapeutic agent for bladder carcinoma is cisplatin with objective responses ranging from 26% to 56%, with complete responses seen in 0%-14%. In a study of 121 patients, MVAC (methotrexate, vinblastine, doxorubicin [Adriamycin] and cisplatin) demonstrated an overall response rate of 72% one half of the responses being complete (Sternberg et al. 1989). The median survival was 13 months. CISCA (cisplatin, doxorubicin, and cyclophosphamide) was compared to MVAC MVAC proved to be superior with a difference in median survival of 82 versus 40 weeks (Logothetis... 

THC is effective in several chemotherapy regimens, including methotrexate and the doxorubicin/cyclophosphamide/fluorouracil combination. Cisplatin treatment, however, is more resistant. Side effects of THC are generally well tolerated, and use may be limited in the elderly or with higher doses. Nabilone is a synthetic cannabinoid that is more effective than prochlorperazine in chemotherapy-induced emesis, including cisplatin. Its side effects are similar to THC. Levonantradol is another synthetic cannabinoid with antiemetic effects, and may be administered orally or intramuscularly. The side effect of dysphoria may limit its use. 

In phase II studies with topotecan alone, there is cytotoxic activity in lung cancer with intermittent dose schedules (33), as well as in lung cancer patients with topoisomerase II refractory disease (34). In advanced head and neck cancer topotecan is well-tolerated and has single-agent activity similar to that of cisplatin, 5-fluorouracil, and methotrexate... 

Morrell LE, Lee YJ, Hurley J, et al. A Phase II trial of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin in the treatment of patients with locally advanced breast carcinoma. Cancer 1998 82 503-511. 

Osiris reported that MSC are able to survive, differentiate and produce hematopoietic cytokines when treated for 24 h with chemotherapeutic agents, such as methotrexate (0.75 or 450 mg/kg) or cisplatin (1 mg/kg), but not doxorubicin (1 mg/kg), suggesting that MSC could be used during the treatment of certain types of cancer [433228]. 

Fig. 3 Venn-diagram for selected compounds interacting with the key MDR-related ABC transporters. MDR-substrate anticancer agents. Abbreviations VCR vincristine, VP-16 etoposide, STER steroids, TAM tamoxiphen, TKI-INHIB tyrosin kinase inhibitors e.g. STI-571, DOX doxorubicine or adriamycin, DNR daunorubicin, EPIR epirubicin, MX mitoxantrone, TOPOT topotecan, iridotecan, BISANT bisanthrone, COLCH colchicin, ACT-D actinomycin D, MYTOM mytomycin, TX methotrexate, CPHAM cyclophosphamide, CHLB chlorambucil, CARM carmustine, LCV leucovorin, HUR hydroxy urea, CISPL cisplatin, TAXOL paclitaxel. (Reproduced from [4])...

Increased risk of myelosuppression with clozapine, azathioprine, cisplatin, methotrexate... 

Conti JA, Scher HI. Acute arterial thrombosis after escalated-dose methotrexate, vinblastine, doxorubicin, and cisplatin chemotherapy with recombinant granulocyte colony-stimulating factor. A possible new recombinant granulocyte colony-stimulating factor toxicity. Cancer 1992 70(ll) 2699-702. 

Forty patients with lung cancer, treated with a combination of cisplatin, mitomycin, vinblastine, doxorubicin, cyclosphosphamide, and methotrexate, had a significant post-treatment increase in fibrinopeptide A and a fall in fibrinolytic activity, reflected by a fall in functional tissue activator this appeared to be cumulative, depending on the extent of drug exposure (184). 

Clinically important, potentially hazardous interactions with altretamine, amikacin, aminoglycosides, antineoplastics, bleomycin, busulfan, carboplatin, carmustine, chlorambucil, cisplatin, corticosteroids, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, docetaxel, doxorubicin, estramustine, etoposide, fludarabine, fluorouracil, gemcitabine, gentamicin, hydroxyurea, idarubicin, ifosfamide, indomethacin, kanamycin, levamisole, lomustine, mechlorethamine, melphalan, mercaptopurine, methotrexate, mitomycin, mitotane, mitoxantrone, neomycin, pentostatin, plicamycin, procarbazine, streptomycin, streptozocin, thioguanine, thiotepa, tobramycin, tretinoin, uracil, vinblastine, vincristine, vinorelbine... 

---