J Aisner

University of Maryland Medical Center, Baltimore, Maryland, United States

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Publications (234)1510.24 Total impact

  • Annals of the New York Academy of Sciences 12/2006; 411(1):161 - 169. · 4.38 Impact Factor
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    ABSTRACT: To evaluate the incidence of thrombocytopenia and bleeding among patients with solid tumors treated intensively with chemotherapy, the records of 1274 patients treated between 1972 and 1980 on protocols known to produce significant myelosuppression were reviewed. Three hundred one patients with solid tumors (breast, lung, melanoma, sarcoma, primary brain, testicular, hypernephroma and others) experienced 5063 days of thrombocytopenia (platelet count < 50,000/ μl) and 670 days of severe thrombocytopenia (platelet count < 20,000/μl). The median number of days thrombocytopenia was 6 (range, 1 -250). There were only 44 episodes of clinically detectable serious bleeding, primarily gastrointestinal (26/44), during thrombocytopenia and all but seven episodes first occurred at platelet counts between 20,000-50,000/ μl. Fifteen of the 44 bleeding episodes were associated with coagulation abnormalities, 24 occurred during serious infection, and 12 occurred at sites of tumors. One hundred forty-seven of the 301 patients (49%) received platelet transfusions. In 86 thrombocytopenic patients with central nervous system (CNS) tumors, there was no evidence of CNS bleeding during thrombocytopenia. Hemorrhagic deaths were uncommon, and of the 12 patients who died of bleeding, 7 had normal counts. There is a very low incidence of significant thrombocytopenia or bleeding among patients with solid tumors treated with combination chemotherapy or experimental agents escalated to maximally tolerated doses. These data suggest that with respect to thrombocytopenic bleeding intensive treatment of patients with solid tumors can be pursued with relative safety utilizing the standard transfusion supportive measures now widely available.
    Cancer 06/2006; 53(3):557 - 562. · 5.20 Impact Factor
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    ABSTRACT: The effect of hydroxyethyl starch (HES) on granulocyte and platelet functions was assessed. No alteration of granulocyte viability, morphology, phagocytic ability, or bactericidal capacity was detected after incubation with 6 per cent HES at 25 C for two hours. Platelet morphology, size distribution, aggregation, nucleotide and serotonin release, and platelet factor-3 availability were also unchanged after exposure to HES. It is concluded that HES has no adverse effect on cell function and appears to be a suitable adjuvant agent for blood cell component collection.
    Transfusion 09/2003; 15(5):473-5. · 3.53 Impact Factor
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    ABSTRACT: To determine whether biochemical modulation with LV (leucovorin) enhances the efficacy of CAF (cyclophosphamide, doxorubicin, and fluorouracil) against metastatic breast cancer. Women with histologically confirmed stage IV breast cancer, Cancer and Leukemia Group B (CALGB) performance status 0 to 2, and no prior chemotherapy for metastatic disease were randomly assigned to receive CAF (cyclophosphamide 500 mg/m2 day 1, doxorubicin 40 mg/m2 day 1, and fluorouracil [FU] 200 mg/m2 intravenous bolus days 1 to 5) with or without LV (LV 200 mg/m2 over 30 minutes days 1 to 5 given 1 hour before FU). Two hundred forty-two patients were randomly assigned to treatment; 124 patients had visceral crisis and 40 patients had a CALGB performance status score of 2. The median follow-up was 6 years. The two study arms were similar with regard to serious adverse events; four patients died from treatment-related causes, two patients on each study arm. Predictive variables for time to treatment failure and survival were visceral disease and performance status. The overall response rate was 29% for CAF versus 28% for CAF plus LV. The median time to treatment failure (9 months) and median survival (1.7 years) did not differ by treatment arm. Modulation of CAF with LV improved neither response rates nor survival among women with metastatic breast cancer, compared with CAF alone. Multivariate analyses confirmed the prognostic importance of performance status and visceral crisis. However, the overall and complete response rates, response durations, time to treatment failure, and survival were the same in the two treatment arms.
    Journal of Clinical Oncology 06/2003; 21(9):1819-24. · 18.04 Impact Factor
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    ABSTRACT: Patients with thymic tumors (thymoma and thymic carcinoma) are known to respond to a variety of chemotherapeutic agents, including single-agent ifosfamide and cisplatin with etoposide. The purpose of this trial was to evaluate the response rate, progression free survival, overall survival, and toxicity of combined etoposide, ifosfamide, and cisplatin (VIP) in patients with advanced thymoma and thymic carcinoma. From July 1995 through February 1997, 34 patients with advanced thymoma or thymic carcinoma were entered on trial to receive etoposide (75 mg/m2 on Days 1-4) ifosfamide (1.2 g/m2 on Days 1-4), and cisplatin (20 mg/m2 on Days 1-4). Cycles were repeated every 3 weeks for four total cycles. Among 28 evaluable patients (pathology review excluded 6 patients), there were no complete responses and 9 partial responses (complete and partial responses combined, 32%; 95% confidence interval, 16-52%). The median follow-up was 43 months (range, 12.8-52.3 months), the median duration of response was 11.9 months (range, < 1-26 months), and the median overall survival was 31.6 months. Based on Kaplan-Meier estimates, the 1-year and 2-year survival rates were 89% and 70%, respectively. The toxicity was predominantly myelosuppression. The VIP regimen has moderate activity in patients with advanced thymic malignancies. However, with limited follow-up, the results of this trial appear to be inferior to other chemotherapy regimens reported in large Phase II trials performed in patients with this disease.
    Cancer 06/2001; 91(11):2010-5. · 5.20 Impact Factor
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    ABSTRACT: Prophylactic cranial irradiation reduces the incidence of brain metastasis in patients with small-cell lung cancer. Whether this treatment, when given to patients in complete remission, improves survival is not known. We performed a meta-analysis to determine whether prophylactic cranial irradiation prolongs survival. We analyzed individual data on 987 patients with small-cell lung cancer in complete remission who took part in seven trials that compared prophylactic cranial irradiation with no prophylactic cranial irradiation. The main end point was survival. The relative risk of death in the treatment group as compared with the control group was 0.84 (95 percent confidence interval, 0.73 to 0.97; P= 0.01), which corresponds to a 5.4 percent increase in the rate of survival at three years (15.3 percent in the control group vs. 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased the rate of disease-free survival (relative risk of recurrence or death, 0.75; 95 percent confidence interval, 0.65 to 0.86; P<0.001) and decreased the cumulative incidence of brain metastasis (relative risk, 0.46; 95 percent confidence interval, 0.38 to 0.57; P<0.001). Larger doses of radiation led to greater decreases in the risk of brain metastasis, according to an analysis of four total doses (8 Gy, 24 to 25 Gy, 30 Gy, and 36 to 40 Gy) (P for trend=0.02), but the effect on survival did not differ significantly according to the dose. We also identified a trend (P=0.01) toward a decrease in the risk of brain metastasis with earlier administration of cranial irradiation after the initiation of induction chemotherapy. Prophylactic cranial irradiation improves both overall survival and disease-free survival among patients with small-cell lung cancer in complete remission.
    New England Journal of Medicine 09/1999; 341(7):476-84. · 54.42 Impact Factor
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    ABSTRACT: New agents with activity in mesothelioma are sorely needed. The Cancer and Leukemia Group B (CALGB) therefore performed a phase II study of high-dose paclitaxel in patients with malignant mesothelioma who had no prior chemotherapy. Thirty-five patients accrued to this multi-institutional phase II study of paclitaxel given as a 24-hour infusion at 250 mg/m2 every three weeks plus filgrastim (G-CSF) 300 mcg subcutaneously days 3-18. There were three (9%) regressions of evaluable disease. The median survival was five months (95% confidence interval (95% CI): 1.9-9.6 months), the one-year survival rate was 14% and the two-year survival rate was 6%. Toxicity was tolerable with one death from pneumonia (without neutropenia) on day 18 and a 23% rate of grade 4 granulocytopenia. The level of activity seen with paclitaxel is similar to that seen in other CALGB trials of the single agents carboplatin, trimetrexate and 5-azacytidine. Future studies of of paclitaxel (at lower doses) in combination with synergistic agents could be considered.
    Annals of Oncology 06/1999; 10(5):597-600. · 7.38 Impact Factor
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    ABSTRACT: To determine the maximum-tolerated dose of paclitaxel with carboplatin with and without filgrastim support in patients with metastatic non-small-cell lung cancer (NSCLC) and to investigate the pharmacokinetics of paclitaxel and carboplatin and correlate these with the pharmacodynamic effects. Thirty-six chemotherapy-naive patients with metastatic NSCLC were entered into this phase I dose-escalation and pharmacokinetic study. Paclitaxel was initially administered as a 24-hour infusion at a fixed dose of 135 mg/m2, and the carboplatin dose was escalated in cohorts of three patients, using Calvert's formula [dose(mg) = area under the concentration time curve (glomerular filtration rate + 25)], to target areas under the concentration time curve (AUCs) of 5, 7, 9, and 11 mg/mL x minute. A measured 24-hour urinary creatinine clearance was substituted for the glomerular filtration rate. Once the maximum-tolerated AUC (MTAUC) of carboplatin was reached, the paclitaxel dose was escalated to 175, 200, and 225 mg/m2. When the paclitaxel dose escalation began, the AUC of carboplatin was reduced to one level below the MTAUC. Myelosuppression was the major dose-limiting toxicity. Thrombocytopenia was observed at a carboplatin AUC of 11 mg/mL x minute after course 2 and thereafter. End-of-infusion plasma paclitaxel concentrations and median duration of time above 0.05 microM were similar in course 1 versus course 2 at the 135 and 175 mg/m2 dose levels. The neutropenia experienced by patients was consistent with that observed in patients who had received paclitaxel alone. Measured carboplatin AUCs were approximately 12% (20% v 3% with course 1 v course 2, respectively) below the desired target, with a standard deviation of 34% at all dose levels. A sigmoid-maximum effect model describing the relationship between relative thrombocytopenia and measured free platinum exposure indicated that patients who received the combination of carboplatin with paclitaxel experienced less severe thrombocytopenia than would be expected from carboplatin alone. Of the 36 patients entered onto the study, one experienced a complete response and 17 had partial responses, for an overall response rate of 50%. The recommended doses of paclitaxel (24-hour infusion) and carboplatin for future phase II studies of this combination are (1) paclitaxel 135 mg/m2 with a carboplatin dose targeted to achieve an AUC of 7 mg/mL x minute without filgrastim support; (2) paclitaxel 135 mg/m2 with a carboplatin dose targeted to achieve an AUC of 9 mg/mL x minute with filgrastim support; and (3) paclitaxel 225 mg/m2 with a carboplatin dose targeted to achieve an AUC of 7 mg/mL x minute with filgrastim support. The regimen of paclitaxel and carboplatin is well-tolerated and has promising activity in the treatment of NSCLC. There is no pharmacokinetic interaction between paclitaxel and carboplatin, but there is a pharmacodynamic, platelet-sparing effect on this dose-limiting toxicity of carboplatin.
    Journal of Clinical Oncology 03/1999; 17(2):676-84. · 18.04 Impact Factor
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    ABSTRACT: To investigate whether dose escalation of megestrol acetate (MA) improves response rate and survival in comparison with standard doses of MA. Three hundred sixty-eight patients with metastatic breast cancer, positive and/or unknown estrogen and progesterone receptors, zero or one prior trial of hormonal therapy, and no prior chemotherapy for metastatic disease were prospectively randomized into three groups. The groups of patients received either MA 160 mg/d (one tablet per day), MA 800 mg/d (five tablets per day), or MA 1,600 mg/d (10 tablets per day). Patient characteristics were well balanced in the three treatment groups. Three hundred sixty-six patients received treatment and were included in the analyses. The response rates were 23%, 27%, and 27% for the 160-mg, 800-mg, and 1,600-mg arms, respectively. Response duration correlated inversely with dose. Median durations of response were 17 months, 14 months, and 8 months for the 160-mg, 800-mg, and 1,600-mg arms, respectively. No significant differences in the treatment arms were noted for time to disease progression or for survival; survival medians were 28 months (low dose), 24 months (mid dose) and 29 months (high dose). The most frequent and troublesome toxicity, weight gain, was dose-related, with approximately 20% of patients on the two higher-dose arms reporting weight gain of more than 20% of their prestudy weight, compared with only 2% in the 160-mg dose arm. With a median follow-up of 8 years, these results demonstrate no advantage for dose escalation of MA in the treatment of metastatic breast cancer.
    Journal of Clinical Oncology 02/1999; 17(1):64-73. · 18.04 Impact Factor
  • International Journal of Radiation OncologyBiologyPhysics 01/1999; 45(3):149-149. · 4.52 Impact Factor
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    ABSTRACT: The current study assessed the psychologic and neuropsychologic functioning of patients with small-cell lung cancer who were randomized in a large clinical trial to receive intensive doxorubicin, cyclophosphamide, etoposide (ACE)/cisplatin, cyclophosphamide, etoposide (PCE) chemotherapy and radiation therapy (RT) to the primary tumor and prophylactic whole-brain irradiation with (regimen I) or without (regimen II) warfarin. Patients' emotional states and cognitive functioning were assessed using the Profile of Mood States (POMS) and Trail Making B Test (Trails B), respectively. Two hundred ninety-five patients completed the POMS and Trails B at pretreatment, 224 patients after the completion of the ACE course of chemotherapy (week 9), and 177 patients after the completion of the PCE chemotherapy and RT (week 17). No differences on the POMS or Trails B measures were found between the two treatment arms as predicted, given that the only difference between the two treatment arms was the presence or absence of warfarin. Analysis of the POMS revealed that, overall, mean scores remained stable over the course of treatment; however, women showed a trend toward higher mean scores, which indicated a higher level of distress, compared with men at the pretreatment assessment. Examination of cognitive functioning, measured by the Trails B, revealed improved performance from baseline to post-ACE chemotherapy, which is consistent with a practice effect, but a significant worsening of Trails B scores post-RT compared with the pre-RT assessments, which is consistent with impaired cognitive functioning because of treatment (P < .0001). Emotional state, measured by the POMS, did not differ between the groups or change significantly over time in this study of small-cell lung cancer patients treated with a combination of chemotherapy and RT plus or minus warfarin. However, the pattern of relatively stable POMS scores and poorer Trails B performance post-RT suggested that this combination of chemotherapy and RT had a negative impact on cognitive functioning.
    Journal of Clinical Oncology 05/1998; 16(5):1954-60. · 18.04 Impact Factor
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    ABSTRACT: In a prior Cancer and Leukemia Group B (CALGB) Phase II trial of patients with advanced, previously untreated mesothelioma, dihydro-5-azacytidine (DHAC) demonstrated a 17% response rate, including 1 complete response, with only mild myelosuppression. This Phase II study (CALGB 9031) was conducted to determine the effectiveness of and toxicities that would result from adding cisplatin to DHAC administered to the same patient population. Thirty-six patients were treated with concurrent DHAC at 1500 mg/m2/day for 5 days by continuous infusion and cisplatin 15 mg/m2 daily for 5 days. Therapy was repeated every 3 weeks. Cisplatin was to be increased to 20 mg/m2 daily in subsequent cycles if toxicity was minimal. Therapy was continued until disease progression or excessive toxicity mandated discontinuation. Overall, 5 objective responses were observed in 29 evaluated patients (objective response rate, 17%). The median duration of response was 6.6 months. Median survival was 6.4 months, with a median time to clinical failure of 2.7 months. The major toxicity noted was significant chest/pericardial pain, as was observed with DHAC alone. There were 2 early deaths of unknown cause on Days 9 and 17 of therapy, respectively. Significant leukopenia was observed in 29% of patients, but there were no neutropenic fevers. The addition of cisplatin to DHAC did not increase the response rate over that observed with DHAC alone in patients with mesothelioma; however, it did increase toxicity, especially leukopenia. This combination is not recommended for further studies involving mesothelioma patients.
    Cancer 05/1998; 82(8):1578-84. · 5.20 Impact Factor
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    ABSTRACT: An increased risk of second primary cancers has been reported in patients who survive small-cell carcinoma of the lung. The treatment's contribution to the development of second cancers is difficult to assess, in part because the number of long-term survivors seen at any one institution is small. We designed a multi-institution study to investigate the risk among survivors of developing second primary cancers other than small-cell lung carcinoma. Demographic, smoking, and treatment information were obtained from the medical records of 611 patients who had been cancer free for more than 2 years after therapy for histologically proven small-cell lung cancer, and person-years of follow-up were cumulated. Population-based rates of cancer incidence and mortality were used to estimate the expected number of cancers or deaths. The actuarial risk of second cancers was estimated by the Kaplan-Meier method. Relative to the general population, the risk of all second cancers among these patients (mostly non-small-cell cancers of the lung) was increased 3.5-fold. Second lung cancer risk was increased 13-fold among those who received chest irradiation in comparison to a sevenfold increase among nonirradiated patients. It was higher in those who continued smoking, with evidence of an interaction between chest irradiation and continued smoking (relative risk = 21). Patients treated with various forms of combination chemotherapy had comparable increases in risk (9.4- to 13-fold, overall), except for a 19-fold risk increase among those treated with alkylating agents who continued smoking. Because of their substantially increased risk, survivors should stop smoking and may consider entering trials of secondary chemoprevention.
    JNCI Journal of the National Cancer Institute 01/1998; 89(23):1782-8. · 14.34 Impact Factor
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    ABSTRACT: Studies by the Veterans Administration Cooperative Studies Program and Cancer and Leukemia Group B (CALGB) suggested that the addition of warfarin to chemotherapy might enhance response and/or survival in small-cell lung cancer (SCLC). This randomized study evaluated the effect of warfarin with chemotherapy and radiation therapy in limited-stage SCLC. Patients were randomized to receive warfarin or no warfarin. All patients received three cycles of doxorubicin, cyclophosphamide, and etoposide (ACE). Cycles 4 and 5 (cisplatin, cyclophosphamide, and etoposide [PCE]) were given concurrently with radiation therapy. Three cycles of ACE were given after chemoradiation therapy, but were discontinued due to a high rate of pulmonary toxicity. There were no significant differences in response rates, survival, failure-free survival, disease-free survival, or patterns of relapse between the warfarin-treated and control groups. In patients treated according to the initial design, an increase in failure-free survival seen with warfarin treatment approached significance (P = .07). Preamendment results, while not significant, did not have superimposable treatment survival curves. A landmark analysis at 8 months showed a median survival time after the landmark for complete responders of 33 months with warfarin treatment compared with < or = 13.75 months for complete or partial responders not treated with warfarin (P = .05). Differences between the complete responders in this preamendment population were not significant (P = .103). Warfarin does not appear to improve outcome significantly in limited-stage SCLC. However, the differences in some variables between populations before the protocol amendment correspond to the favorable effects of anticoagulants observed in previous studies.
    Journal of Clinical Oncology 11/1997; 15(11):3378-87. · 18.04 Impact Factor
  • Lung Cancer 08/1997; 18:63-63. · 3.39 Impact Factor
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    ABSTRACT: Combined chemoradiotherapy is superior to radiotherapy alone for stage III and IV squamous cell carcinoma of the head and neck, and concurrent use of both offers the advantage of synergistic interactions. Our prior trial demonstrated the ease and convenience of administering carboplatin during radiotherapy. Since paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has activity in squamous cell carcinoma of the head and neck and can act synergistically with both radiotherapy and platinum drugs, we initially added paclitaxel at 45 mg/m2/wk to carboplatin given at 100 mg/m2 during radiotherapy given at conventional fractions. The initial dose of paclitaxel was subsequently reduced to 40 mg/m2/wk. Thirteen of 18 patients entered so far have sufficient follow-up data; 12 are assessable for toxicity and 11 are assessable for response. One died early of progressive disease, two achieved a complete response, six achieved a partial response, and two had stable disease. Toxicities have so far been manageable for the 76 weekly doses administered. Chemotherapy dose reduction was needed in 10 patients. For the planned 100 doses of chemotherapy, 53 (53%) were administered as planned, 23 (23%) were reduced, and 24 (24%) were withheld due to neutropenia or mucositis. There were no toxic deaths, and no patient stopped therapy for toxicity. Paclitaxel/carboplatin can be administered during radiotherapy for squamous cell carcinoma of the head and neck with acceptable toxicities, and further accrual is needed to evaluate the effect of this combination.
    Seminars in Oncology 03/1997; 24(1 Suppl 2):S2-78-S2-80. · 4.33 Impact Factor
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    ABSTRACT: Based on superior results observed with combined-modality therapy over radiotherapy alone and on the authors' previous work with carboplatin and standard daily thoracic radiotherapy in patients with advanced, unresectable non-small cell lung cancer, a phase II study was designed to incorporate radiosensitizing doses of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) into the carboplatin/radiotherapy regimen, to improve the therapeutic index and define the toxicities. Thirty-two patients have been entered. Paclitaxel 45 mg/m2/wk was administered over 3 hours prior to carboplatin (100 mg/m2/wk) and thoracic radiotherapy (1.8 Gy/d 5 days a week; total dose, 60 to 65 Gy). No grade 4 toxicities occurred. Seven patients had chemotherapy doses delayed because of grade 3 neutropenia, and one patient had grade 3 mucositis/esophagitis that required hospitalization. Median survival has not yet been reached, and all patients are being followed. These preliminary data demonstrate the feasibility of combined concurrent chemoradiotherapy, with acceptable toxicities. Further investigation is needed to optimize carboplatin dosage with adaptive control using formulas based on pharmacokinetics and pharmacodynamics. Full-dose induction chemotherapy regimens to maximize the systemic effects of chemotherapy should precede concurrent chemoradiotherapy in future studies.
    Seminars in Oncology 01/1997; 23(6 Suppl 16):113-6. · 4.33 Impact Factor
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    ABSTRACT: Given their known activity against non-small cell lung cancer, paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin were combined in this phase I study of patients with metastatic disease to determine the maximum tolerated dose and the dose-limiting toxicity of the combination. The initial dose of paclitaxel was fixed at 135 mg/m2 given as a 24-hour infusion with carboplatin administered in escalating doses in cohorts using Calvert's formula-dose (mg) = target AUC x (GFR + 25), where AUC is area under the concentration-time curve and GFR is glomerular filtration rate-based on target AUCs of 5, 7, 9, or 11 mg/mL.min. Dose escalations were based on cycle 1 toxicities. Filgrastim was not administered with the first cycle until two or more patients developed grade 4 or febrile neutropenia at the preceding dose level. Dose-limiting toxicity occurred in two patients at level 2 (cycle 1), and filgrastim was administered thereafter for the next four dose levels. Grade 4 thrombocytopenia was seen at level 4; thus, the carboplatin dose was de-escalated thereafter, and the paclitaxel dose escalated. Rare nonhematologic toxicities include fatigue, diarrhea, and nausea and vomiting. Among the first 30 patients, one had a complete response and 14 had partial responses, for an overall response rate of 50%. The combination of paclitaxel and carboplatin is active in non-small cell lung cancer, and the recommended phase II dose without filgrastim support is paclitaxel 175 mg/m2 via a 24-hour infusion with the carboplatin dose targeted to achieve an AUC of 7 mg/ mL.min.
    Seminars in Oncology 11/1996; 23(5 Suppl 12):19-21. · 4.33 Impact Factor
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    ABSTRACT: We studied the pharmacokinetics of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin administered in combination to 21 patients with advanced non-small cell lung cancer. Paclitaxel was administered as a 24-hour intravenous infusion at doses of 135 to 200 mg/m2. Carboplatin, dosed to a target area under the concentration-time curve of 5, 7, 9, or 11 mg/mL.min, was administered as a 20-minute infusion immediately following paclitaxel. Neither the paclitaxel concentrations at the end of the infusion nor the terminal elimination of paclitaxel, as assessed by the duration of time that plasma paclitaxel concentrations were 0.05 mumol/L or greater, were different compared with historical data of paclitaxel as a single agent. Thus, we concluded that carboplatin had no perceived effect on the pharmacokinetics of paclitaxel in this schedule. The observed areas under the concentration-time curves for carboplatin were consistently 10% to 15% less than the target values. Although this may indicate a possible interaction between paclitaxel and carboplatin, it also may have been a result of inadequate assessment of glomerular filtration rate, which was used to determine the carboplatin dose.
    Seminars in Oncology 11/1995; 22(5 Suppl 12):1-4; discussion 5-7. · 4.33 Impact Factor
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    ABSTRACT: Sequential chemotherapy and radiotherapy offer considerable improvements in the care of patients with locally advanced non-small cell lung cancer (NSCLC) and squamous cell carcinoma of the head and neck (SCCHN). Improved survival for lung cancer and organ preservation in head and neck cancer have occurred with this approach, but local control remains a problem. Concurrent chemotherapy and radiotherapy can potentially improve both local control and control of micrometastases. We previously showed that concurrent carboplatin plus radiotherapy is a useful potential treatment for advanced NSCLC and SCCHN, producing good local control and acceptable toxicity. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has recently demonstrated strong single-agent activity against both NSCLC and SCCHN. Paclitaxel has also shown favorable interactions with radiotherapy and with platinum compounds. We therefore added weekly paclitaxel at 45 mg/m2 given after premedication and before carboplatin (100 mg/m2) weekly during concurrent standard-dose radiotherapy. Twenty patients (seven with SCCHN and 13 with NSCLC) have been treated (38 and 73 weekly doses, respectively). Toxicities have been manageable with delay or dose reduction in five and eight patients, respectively, for SCCHN and NSCLC. Based on these toxicities paclitaxel dose has been reduced to 40 mg/m2/wk. Plasma pharmacokinetics have shown that concurrent carboplatin and radiotherapy do not alter the pharmacokinetic behavior of paclitaxel compared with single-agent data. Concurrent therapy with carboplatin, paclitaxel, and radiotherapy is feasible on this schedule. Further case accrual to assess efficacy is ongoing.
    Seminars in Oncology 11/1995; 22(5 Suppl 12):17-21. · 4.33 Impact Factor

Publication Stats

4k Citations
1,510.24 Total Impact Points

Institutions

  • 1979–2003
    • University of Maryland Medical Center
      • Department of Medicine
      Baltimore, Maryland, United States
    • University of California, Los Angeles
      Los Angeles, California, United States
  • 1999
    • Institut de Cancérologie Gustave Roussy
      Île-de-France, France
  • 1990–1999
    • University of Chicago
      • Department of Medicine
      Chicago, IL, United States
    • St. Mary Medical Center
      Long Beach, California, United States
  • 1997
    • Dartmouth–Hitchcock Medical Center
      Lebanon, New Hampshire, United States
  • 1979–1995
    • University of Maryland, Baltimore
      • Department of Medicine
      Baltimore, Maryland, United States
  • 1993
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
  • 1987–1992
    • University of Missouri
      Columbia, Missouri, United States
  • 1989
    • Albert Einstein College of Medicine
      • Oncology
      New York City, NY, United States
  • 1981–1988
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • Loyola University Maryland
      Baltimore, Maryland, United States
    • NCI-Frederick
      Maryland, United States
  • 1976–1979
    • National Cancer Institute (USA)
      Maryland, United States