Carboplatin therapy

Hz. The overall conclusion is that with low-dose, short-schedule, carboplatin therapy, routine audiometry is not justified (152). 

Audiological testing has been recommended for patients receiving high-dose carboplatin therapy, following hearing problems in a series of 10 patients with ovarian cancer (156). 

Lauer AK, Wobig JL, Shults WT, Neuwelt EA, Wilson MW. Severe ocular and orbital toxicity after intracarotid etoposide phosphate and carboplatin therapy. Am J Ophthalmol 1999 127(2) 230-3. 

Recommendation 4. For the prevention of delayed emesis after cisplatin therapy in adults, dexamethasone with metoclopramide or a SSRI is recommended. Thechoice of agent should be based on patient-specific factors and cost. For delayed emesis after cyclophosphamide, doxorubicin, or carboplatin therapy, a SSRI with dexamethasone is recommended. In pediatric patients, chlorpromazine, lorazepam, or a SSRI can be used in combination with a corticosteroid. 

It proved to be disappointing, however, during initial Phase III trials. Eli Lilly was sponsoring Phase III trials to further explore its efficacy in combination with ohemotherapeutic agents for lung cancer, but enrollment was terminated in March 2003, when a Phase III trial suggested that aprinocarsen did not have an added survival benefit when combined with paclitaxel and carboplatin therapy in patients with nonsmallcell lung cancer (28). 

Adduct Levels Before/After Carboplatin Therapy ... 

Early clinical studies clearly demonstrated that cisplatin could be administered safely and concurrently with radiation therapy (73-75). Early clinical trials that demonstrated the promise of the combination of cisplatin and radiation therapy included the treatment of brain tumors (76,77), head and neck tumors (78), malignant melanoma (79), and bladder cancer (80). Early clinical trial integrating carboplatin administration with radiation therapy was carried out in patients with locally advanced nonsmall cell lung cancer (NSCLC) (81). A hypothesis put forth by Coughlin and colleagues (81) was that the best clinical outcomes would be achieved with the combination of cisplatin and radiation therapy in tumors that were responsive to cisplatin. 

The Southwest Oncology Group (SWOG) conducted a phase II trial with continuous thoracic radiation to a total dose of 61 Gy and simultaneous daily cisplatin (5 mg/m2) and found acceptable toxicity (130). Another trial utilized a split-course of thoracic radiation therapy to a total dose of 50 Gy and simultaneous daily continuous infusion cisplatin (5 mg/m2) and found a 35 % 2-yr survival rate with relatively mild toxicity (131). Weekly doses of carboplatin were administered with continuous thoracic irradiation to a total dose of 60 Gy in a phase II trial that resulted in a 45% response rate (132). 

Douple EB, Richmond RC, O Hara J A, Coughlin CT. Carboplatin as a potentiator of radiation therapy. Cancer Treat Revs 1985 12(Suppl A) lll-124. 

Jeremie B, Shibamoto Y, Stanisavljevic B, Milojevic L, Milicic B, Nikolie N. Radiation therapy alone or with concurrent low-dose either cisplatin or carboplatin in locally advanced unresectable squamous cell carcinoma of the head and neck a prospective randomized trial. Radiotherap Oncol 1997 43 29-37. 

Highley MS, Calvert AH. Chnical experience with cisplatin and carboplatin. In (Kelland LR, Farrell N, eds) Platinum-Based Drugs in Cancer Therapy 2000 Humana Press Inc. Totowa, NJ pp. 171-194. 

Socinski et al. have reported on their phase I/II experience with dose-escalated thoracic radiation in the setting of a combined modality approach to locally advanced NSCLC (55,64). Two cycles of carboplatin and paclitaxel (AUC 6 and 225 mg/m2/3h q21d) were followed on d 43 by weekly carboplatin and paclitaxel (AUC 2 and 45 mg/ m2/3h x 6) and thoracic radiotherapy (TRT), 50 Gy was delivered to the prechemotherapy tumor volume and areas of suspected microscopic spread in the mediastinum with a 1.0-2.0 cm margin. Boost volumes included the primary tumor volume and all radiographically positive nodes with a 1.0 cm margin. The total dose of radiation was escalated through four cohorts of patients 60,66,70,74 Gy without reaching any of the planned toxicity endpoints. The overall response to the therapy was 50% (3% CR, 47%... 

Socinski M A, Rosenman JG, Schell MJ, et al. Induction carboplatin/paclitaxel followed by concurrent carboplatin/paclitaxel and dose-escalating conformal thoracic radiation therapy in unresectable stage IIIA/B nonsmall-cell lung carcinoma a modified Phase I trial. Cancer 2000 89(3) 534-542. 

Choy H, Akerley W, Safran H, et al. Multiinstitutional phase II trial of paclitaxel, carboplatin, and concurrent radiation therapy for locally advanced non-small-cell lung cancer. J Clin Oncol 1998 16(10) 3316-3322. 

Choy H, DeVore RF, Porter LL, et al. Phase I trial of outpatient weekly docetaxel (DTX) Carboplatin (CBDCA) and concurrent thoracic radiation therapy (TRT) for stage III unresectable non-small-cell lung cancer A Vanderbilt Cancer Center Affiliate Network (VCCAN) Trial. Pro Am Soc Clin Oncol 1999 18 475a (abstract 1833). 

K. Radiation therapy and concomitantpaclitaxel/carboplatin chemotherapy formuscle invasive transitional cell carcinoma of the bladder a well-tolerated combination. Int J Cancer 2000 90(5) 281-286. 

Meluch AA, Hainsworth JD, Gray JR, et al. Preoperative combined modality therapy with paclitaxel, carboplatin, prolonged infusion 5-fluorouracil, and radiation therapy in localized esophageal cancer preliminary results of a Minnie Pearl Cancer Research Network phase II trial. Cancer J Sci Am 1999 5 (2) 84-91. 

Other trials attempted to improve the results of sequential chemoradiation by using newer ChT agents and/or intensifying the RT component by the use of accelerated fractionation, based on the success of the British CHART regimen. A phase II trial of paclitaxel and carboplatin followed by hyperfractionated accelerated radiation therapy (HART) to... 

Jeremic B, Shibamoto Y, Acimovic L, et al. Hyperfractionated radiation therapy with or without concurrent low-dose daily carboplatin/etoposide for stage M non-small cell lung cancer a randomized study. J Clin Oncol 1996 14 1065-1107. 

Herbst RS, Takeuchi H, Teicher BA. Paclitaxel/carboplatin administration along with antiangiogenic therapy in non-small-cell lung and breast carcinoma models. Cancer Chem Pharm 1998,41 497-504. 

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