Irinotecan + cisplatin

CAV, cyclophosphamide, doxorubicin, vincristine EC, etoposide carboplatin EP, etoposide cisplatin IC, irinotecan, cisplatin. See Table 87M for doses and schedules. 

Irinotecan + cisplatin Mixture of two liposomes Small-cell lung cancer... 

BCRP (ABCG2) Cisplatin, folate, methotrexate, mitoxantrone, topotecan, irinotecan, steroids (cholesterol, testosterone, progesterone), certain chlorophyll metabolites, and others... 

Platinum regimens are also the treatment of choice in extensive disease, and many studies have failed to show superiority to the EP regimen as first-line treatment. A combination of irinotecan and cisplatin in one Japanese study demonstrated an increased median survival time by approximately 3 months... 

Combination studies of olaparib are being explored clinically with a number of agents, including irinotecan, dacarbazine, carboplatin, gemcitabine, doxorubicin, cisplatin, and topotecan. 

Cisplatin 30 mg/m2 IV day 1 Irinotecan 65 mg/m2 IV days 1 and 8 Repeat cycle every 3 weeks1... 

The most frequently used regimen is cisplatin or carboplatin combined with etoposide. Irinotecan in combination with cisplatin has also been shown to be active (see Table 63-1). Overall response rates and survival durations are generally superior for patients with limited stage versus those with extensive stage disease. 

Han, J. Y., Lim, H. S., Shin, E. S., et al. (2006) Comprehensive analysis of UGTIA polymorphisms predictive for pharmacokinetics and treatment outcome in patients with non-small-ceU lung cancer treated with irinotecan and cisplatin. J. Clin. Oncol. 24, 2237-2244. 

Kobayashi K, Shinbara A, Kamimura M, et al. Irinotecan (CPT-11) in combination with weekly administration of cisplatin (CDDP) for non-small-cell lung cancer. Cancer Chemother Pharmacol 1998 42(1 ) 53—58. 

Irinotecan is an active chemotherapeutic agent that has been used in esophageal cancer and is also a potent radiosensitizer. In vitro studies have shown activity in esophageal cancer cell lines. A Phase I study has demonstrated its safety and tolerability with cisplatin. Phase I/II studies are currently underway determining the maximum tolerated weekly dose of irinotecan combined with concurrent radiation for locally advanced esophageal cancer (MSKCC 99081). 

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,... 

Oxaliplatin is a third generation diaminocyclohexane platinum analog. Its mechanism of action is identical to that of cisplatin and carboplatin. However, it is not cross-resistant to cancer cells that are resistant to cisplatin or carboplatin on the basis of mismatch repair defects. This agent was recently approved for use as second-line therapy in metastatic colorectal cancer following treatment with the combination of fluorouracil-leucovorin and irinotecan, and it is now widely used as first-line therapy of this disease as well. Neurotoxicity is dose-limiting and characterized by a peripheral sensory neuropathy, often triggered or worsened upon exposure to cold. While this neurotoxicity is cumulative, it tends to be reversible—in contrast to cisplatin-induced neurotoxicity. 

Patients with small cell lung cancer (the most aggressive type) show the best responses to platinum-based combination regimens, including cisplatin and etoposide or cisplatin and irinotecan. The topoisomerase I inhibitor topotecan is used as second-line monotherapy in patients who have failed a platinum-based regimen. 

In 10 studies the corresponding clinical study protocol stipulated that cetuximab was to be given in combination with a chemotherapeutic agent (irinotecan, paclitaxel, gemcitabine, cisplatin, carboplatin, or doxorubicin) or in combination with radiation therapy. 

The possible impact of co-administered chemotherapies and radiation therapy on the PK of cetuximab was furthermore assessed using the population PK approach, as described in Section 14.6. The co-administered chemotherapies included cisplatin, carboplatin, paclitaxel, doxorubicin, irinotecan, and gemcitabine. The results of the analysis indicate that neither the co-administered chemotherapies nor radiation therapy had a significant impact on the PK of cetuximab. This finding suggests that the potential for PK-based drug-drug interactions with cetuximab is low. 

Cisplatin 30 mg/m IV day I Irinotecan 65 mjynrT IV days I and 8 Repeat cycle every 3 weeks ... 

The most frequently used regimen is cisplatin or carboplatin combined with etoposide. Irinotecan in combination with cisplatin has also been... 

Masuda N, Fukoka M, Negro S, et al. Randomized trial comparing cisplatin (CDDP) and irinotecan (CPT-11) versus CDDP and vindesine (VDS) versus CPT-11 alone in advanced nonsmall cell lung cancer (NSCLC), a multicenter phase III study. Proc Am Soc Clin Oncol 1999 18 1774 (Abstract). 

Noda K, Nishiwaki Y, Kawahara M, et al. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 2002 346 85-91. 

Higher response rates are seen when 5-FU is used in combination with other agents, such as cyclophosphamide and methotrexate (breast cancer), cisplatin (head and neck cancer), and with oxaliplatin or irinotecan in colon cancer. The combination of 5-FU and oxaliplatin or irinotecan has become the standard first-line treatment for patients with metastatic colorectal cancer. The use of 5-FU in combination regimens has improved survival in the adjuvant treatment for breast cancer, and with oxaliplatin and leucovorin, for colorectal cancer. 5-FU also... 

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