Seminars in oncology
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Both gemcitabine (2',2'-difluorodeoxycytidine; dFdC) and cisplatin (cis-diammine dichloroplatinum; CDDP) are active against several solid malignancies, including ovarian cancer and head and neck squamous cell carcinoma. Because of differences in mechanisms of action and toxicity profiles, combination of the two drugs has enormous clinical potential. We studied possible synergism between the drugs: in vitro using three variants of the human ovarian cancer cell line A2780, and in vivo using gemcitabine- and cisplatin-sensitive and -resistant tumors, the head and neck cancer xenografts HNX-22B and HNX-14C and the murine syngeneic colon 26-10 tumor. ⋯ Cisplatin, injected 4 hours before or after gemcitabine, was equally active as the simultaneous schedule in HNX-22B tumors, but more toxic. In conclusion, the combination of gemcitabine and cisplatin can be synergistic in vitro and at least additive in vivo; this synergism is schedule dependent. The mechanism cannot be explained by gemcitabine triphosphate accumulation or DNA damage studies.
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Seminars in oncology · Aug 1995
Randomized Controlled Trial Comparative Study Clinical TrialDose-finding and sequencing study of paclitaxel and carboplatin in non-small cell lung cancer.
A dose-finding study was set up to identify the optimal dose of the combination of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin for phase II studies in patients with advanced chemotherapy-naive non-small cell lung cancer (NSCLC). The influence of drug sequence on the toxicity and pharmacokinetics of both agents was also assessed. To develop an ambulatory regimen for palliation of advanced NSCLC, paclitaxel was infused over 3 hours with standard premedication and carboplatin over 30 minutes. ⋯ At the highest paclitaxel dose (250 mg/m2 with carboplatin 350 mg/m2) a toxic death due to severe leukopenia, thrombocytopenia, and hemorrhage occurred. Safe doses for phase II trials in untreated NSCLC are 200 mg/m2 paclitaxel with 300 mg/m2 carboplatin. Of 50 evaluable patients, five of the six major responses were observed at paclitaxel doses of 175 mg/m2 and above, which suggests a dose-response relationship for paclitaxel in NSCLC.
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Allogeneic BMT and IFN-A-based therapy have undoubtedly changed the natural history of CML. Despite these advances, many patients still die from their disease. Most patients do not qualify for an allogeneic BMT either because of age or lack of an appropriate donor, and only a fraction of patients achieve a complete cytogenetic remission with IFN-A-based therapy. ⋯ Investigators in the field must decide whether to continue randomized trials of IFN-A versus conventional chemotherapy, or to explore strategies that may enhance the effect of IFN-A-based therapy. Only when the durable cytogenetic response rates with IFN-A combinations increase to 40% or 50% will it be of value to proceed to phase III trials. Further understanding in the basic biology of CML and the effect of IFN-A in this disease will also provide clues to improving therapy with the goal of obtaining long-term disease control and cures in the majority of patients with the least burden of therapy.
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CGL is a highly specific disease that is defined by strict hematologic parameters that include a pathognomonic differential leukocyte count. Usually CGL is accompanied by the presence, in bone marrow cells, of the Ph chromosome, the first chromosomal anomaly to be regularly associated with a human neoplastic disease. CGL is predominantly a disease of the productive middle years of life, which maximizes its adverse impact on family life and family economics. ⋯ Also considered are the less frequent but important atypical presentations of CGL. The symptoms and complaints, findings on examination, complications and hematologic findings may depart from the typical case in a bewildering variety of ways, so that the diagnosis may be difficult, indeed, CGL is generally not the initial diagnosis that is made. When the patient with CGL has received treatment, it is usual for he or she to become asymptomatic, with no abnormal physical signs.(ABSTRACT TRUNCATED AT 400 WORDS)
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Seminars in oncology · Aug 1995
Clinical TrialPaclitaxel by 24- or 1-hour infusion n combination with carboplatin in advanced non-small cell lung cancer: the Fox Chase Cancer Center experience.
A phase II trial of combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin included 54 chemotherapy-naive patients with advanced non-small cell lung cancer. Eligibility mandated Eastern Cooperative Oncology Group performance status of 0 or 1 and adequate hematologic, renal, and hepatic function. Paclitaxel 135 mg/m2 over 24 hours preceded carboplatin dosed to an area under the concentration-time curve of 7.5. ⋯ Major nonhematologic toxicities include myalgias and arthralgias (54%) and fatigue and neuropathy (78%), the latter cumulative and progressive over successive cycles. Preliminary data suggest comparable activity for the 1- and 24 hour paclitaxel infusions in combination with carboplatin. The more severe neuropathy of the 1-hour paclitaxel/carboplatin combination may be related to the paclitaxel dosing schema (175 mg/m2 to as high as 280 mg/m2).(ABSTRACT TRUNCATED AT 400 WORDS)