Biomedical subjects

K M Pisters

Publications and source records attributed to K M Pisters.

At least 19 recordsLinked to original sources

PubMed2001

Phase I trial of oral green tea extract in adult patients with solid tumors.

PURPOSE: This trial was designed to determine the maximum-tolerated dose, toxicity, and pharmacology of oral green tea extract (GTE) once daily or three times daily. PATIENTS AND METHODS: Cohorts of three or more adult cancer patients were administered oral GTE with water after meals one or three times daily for 4 weeks, to a maximum of 6 months, depending on disease response and patient tolerance. Pharmacokinetic analyses were encouraged but optional. RESULTS: Dose levels of 0.5 to 5.05 g/m(2) qd and 1.0 to 2.2 g/m(2) tid were explored. A total of 49 patients were studied. PATIENT CHARACTERISTICS: median age, 57 years (range, 27 to 77 years); 23 patients were women (47%); 98% had a Zubrod PS of 1%; 98% had PS of 1; and 21 had non-small-cell lung, 19 had head & neck cancer, three had mesothelioma, and six had other. Mild to moderate toxicities were seen at most dose levels and promptly reversed on discontinuation of GTE. Dose-limiting toxicities were caffeine related and included neurologic and gastrointestinal effects. The maximum-tolerated dose was 4.2 g/m(2) once daily or 1.0 g/m(2) three times daily. No major responses occurred; 10 patients with stable disease completed 6 months of GTE. Pharmacokinetic analyses found accumulation of caffeine levels that were dose dependent, whereas epigallocatechin gallate levels did not accumulate nor appear dose related. CONCLUSION: A dose of 1.0 g/m(2) tid (equivalent to 7 to 8 Japanese cups [120 mL] of green tea three times daily) is recommended for future studies. The side effects of this preparation of GTE were caffeine related. Oral GTE at the doses studied can be taken safely for at least 6 months.

Administration, Oral↗

PubMed2001

Preoperative chemotherapy for lung cancer does not increase surgical morbidity.

BACKGROUND: Preoperative chemotherapy (C+S) for non-small cell lung cancer (NSCLC) has increased in an attempt to improve survival. Patients receiving C+S potentially may have an increase in postoperative morbidity and mortality compared with surgery alone (S). We reviewed our experience with C+S and S in a tertiary referral center. METHODS: Three hundred eighty consecutive patients underwent lobectomy or greater resection for NSCLC between August 1, 1996, and April 30, 1999: 335 patients (259 S; 76 C+S) were analyzed; 45 additional patients were excluded for prior NSCLC, other chemotherapy for other malignancy, or radiation. We compared morbidity and mortality overall, and by subset analysis (clinical stage, pathological stage, procedure, and by protocol use) for both C+S and S patients. RESULTS: Demographics, comorbidities, and spirometry were similar. We noted no significant difference in overall or subset mortality or morbidity including pneumonia, acute respiratory distress syndrome, reintubation, tracheostomy, wound complications, or length of hospitalization. CONCLUSIONS: C+S did not significantly affect morbidity or mortality overall, based on clinical stage, postoperative stage, or extent of resection. The potential for enhanced survival in resectable NSCLC justifies continued study of C+S.

Aged↗

PubMed2001

Adjuvant and neoadjuvant therapy for early stage non-small cell lung cancer.

Lung cancer is the number one cause of cancer-related death in both men and women in the United States. Non-small cell lung cancer accounts for approximately 85% of these cases. Despite complete resection, long-term survival for patients with operable disease remains poor. Studies exploring postoperative chemotherapy have not shown improved survival. Preoperative chemotherapy has shown promise in stage III disease and is currently under investigation for patients with early stage non-small cell lung cancer.

Antineoplastic Agents↗

PubMed2001

ZD1839 (Iressa) in non-small-cell lung cancer.

The epidermal growth factor receptor (EGFR) signaling pathway plays an important role in a number of processes that are key to tumor progression, including cell proliferation, angiogenesis, metastatic spread, and inhibition of apoptosis. EGFR is expressed or overexpressed in non-small-cell lung cancer (NSCLC), and EGFR-mediated growth has been associated with advanced disease and poor prognosis in NSCLC patients. ZD1839 (Iressa) is an orally active, selective EGFR-tyrosine kinase inhibitor that blocks EGFR signal transduction. In preclinical studies using NSCLC cell lines, ZD1839 has been shown to inhibit tumor cell growth. In addition, ZD1839, as monotherapy and in combination with commonly used cytotoxic agents, has produced growth delay in NSCLC human xenografts. Preliminary results from phase I trials in patients with advanced disease have shown that ZD1839 has excellent bioavailability, an acceptable tolerability profile, and promising clinical activity in patients with a variety of tumor types, particularly in NSCLC. ZD1839 is currently in phase III clinical development for the treatment of advanced NSCLC.

Journal Article↗

PubMed2001

Treatment of stage I lung cancer.

This article reviews changes in the roles of surgeons, medical oncologists, and radiation oncologists that have occurred over the past 20 years. A gradual evolution will certainly continue over the next several decades in the multidisciplinary quest to improve the dismal survival results.

Carcinoma, Non-Small-Cell Lung↗

PubMed2001

Phase I and pharmacological study of two schedules of the antifolate edatrexate in combination with cisplatin.

The antifolate edatrexate has shown moderate activity against cancers of the head and neck and non-small cell lung cancer, as has cisplatin. Edatrexate demonstrates synergy with cisplatin in transplanted tumor models. This Phase I study was designed to evaluate two schedules of administration of cisplatin in combination with escalating doses of edatrexate, in a population consisting mainly of patients with these two cancers. The starting dose of edatrexate was 40 mg/m2. Dose escalation was to occur in 10-mg/m2 increments; the planned maximum dose level for study was 80 mg/m2. A total of 39 patients were registered. Eleven were treated on schedule A: cisplatin 120 mg/m2 every 4 weeks, and edatrexate weekly. Twenty-eight patients were assigned to schedule B: cisplatin 60 mg/m2 and edatrexate, both given every 2 weeks. On schedule A, the maximum tolerated dose of weekly edatrexate was 40 mg/m2, with dose-limiting toxicities of leukopenia, mucositis, and renal insufficiency. On schedule B, the maximum tolerated dose of biweekly edatrexate was 80 mg/m2, with leukopenia and mucositis as dose limiting. For schedule A, pharmacokinetic studies suggested a possible effect of cisplatin on the day 8 clearance of edatrexate. Studies on patients on schedule B did not show a clear effect of cisplatin on the day 15 edatrexate clearance. On schedule A, 5 of 9 evaluable patients had major responses (1 complete); whereas on schedule B, 8 of 25 patients had major responses (1 complete). Responses were seen in both head and neck and non-small cell lung cancer patients. For Phase II studies, use of cisplatin 60 mg/m2 and edatrexate 80 mg/m2, both given biweekly, is recommended.

Adult↗

PubMed2000

Induction chemotherapy before surgery for early-stage lung cancer: A novel approach. Bimodality Lung Oncology Team.

OBJECTIVE: This phase II trial assessed the feasibility, as measured by response rate, toxicity, resectability rate, and surgical morbidity and mortality rates, of perioperative paclitaxel and carboplatin chemotherapy in patients with early-stage non-small cell lung carcinoma. METHODS: All patients required negative mediastinoscopy results and adequate medical parameters to undergo induction chemotherapy and an operation. Superior sulcus patients were excluded. Chemotherapy consisted of paclitaxel 225 mg/m(2) over 3 hours and carboplatin (area under the curve = 6) every 21 days for 2 cycles preoperatively. Three postoperative cycles of chemotherapy were planned for patients undergoing complete resection. RESULTS: Between June 1996 and July 1998, 94 patients were entered into the study. Sixty-five (69%) were men, and the median age was 64 years (range, 34-79 years). After induction chemotherapy, 53 of 94 (56%; 95% confidence interval, 46%-67%) had a major objective response, 88 (94%) underwent surgical exploration, and 81 (86%; 95% confidence interval, 78%-92%) underwent complete resection. Reasons for not undergoing an operation included disease progression (n = 3), clinically unresectable status (n = 1), death (n = 1), and patient lost to follow-up (n = 1). Two postoperative deaths occurred. Six (6%; 95% confidence interval, 0%-13%) pathologic complete responses were observed. Ninety (96%) patients received the planned preoperative chemotherapy versus 45% receiving postoperative chemotherapy. No unexpected chemotherapy or surgical morbidity occurred. The 1-year survival is currently estimated at 85%, and the median survival has not yet been reached. CONCLUSIONS: Induction chemotherapy with paclitaxel and carboplatin is feasible and produces a high response rate with acceptable morbidity and mortality rates in early-stage non-small cell lung carcinoma. A prospective randomized trial comparing 3 cycles of induction chemotherapy and surgery with surgery alone in early-stage non-small cell lung carcinoma is planned.

Adult↗

PubMed2000

Cellular and humoral immune responses to adenovirus and p53 protein antigens in patients following intratumoral injection of an adenovirus vector expressing wild-type. P53 (Ad-p53).

The immune responses of 10 patients with advanced non-small cell lung cancer receiving monthly intratumoral injections of a recombinant adenovirus containing human wild-type p53 (Ad-p53) to adenovirus and transgene antigens were studied. The predominate cellular and humoral immune responses as measured by lymphocyte proliferation and neutralizing antibody (Ab) formation were to adenovirus serotype 5 vector antigens, with increased responses in posttreatment samples. Consistent alterations in posttreatment cellular and humoral immune responses to p53 epitopes were not observed, and cytotoxic Abs to human lung cancer cells were not generated. Patients in this study had evidence of an antitumoral effect of this treatment with prolonged tumor stability or regression; however, neither Abs to p53 protein nor increased lymphocyte proliferative responses to wild-type or mutant p53 peptides have been consistently detected.

Adenoviridae↗

PubMed2000

The role of chemotherapy in early-stage (stage I and II) resectable non-small cell lung cancer.

For patients with stage I or II non-small cell lung cancer (NSCLC), surgical resection is considered the standard of care. Although surgery achieves long-term survival in many patients, a significant proportion experience locoregional or distant recurrence. Five-year survival rates after resection for stage I and II NSCLC range from 38% (T3 N0) to 67% (T1 N0). Efforts at improving survival for early-stage NSCLC patients have focused on the use of chemotherapy administered postoperatively (adjuvant) or preoperatively (neoadjuvant or induction) to eradicate micrometastatic disease. The majority of trials examining adjuvant chemotherapy have not found a survival benefit. A meta-analysis examining the role of chemotherapy in the treatment of NSCLC found a 5% absolute improvement in 5-year survival associated with the use of adjuvant cisplatin-based chemotherapy (P =.08). Chemotherapy administered before surgery or definitive irradiation has improved survival rates in patients with stage III NSCLC. The role of induction chemotherapy in stage I and II NSCLC is currently under investigation.

Carcinoma, Non-Small-Cell Lung↗

PubMed2000

Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer.

PURPOSE: To determine the safety and tolerability of adenovirus-mediated p53 (Adp53) gene transfer in sequence with cisplatin when given by intratumor injection in patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with advanced NSCLC and abnormal p53 function were enrolled onto cohorts receiving escalating dose levels of Adp53 (1 x 10(6) to 1 x 10(11) plaque-forming units [PFU]). Patients were administered intravenous cisplatin 80 mg/m(2) on day 1 and study vector on day 4 for a total of up to six courses (28 days per course). Apoptosis was determined by the terminal deoxynucleotidyl- transferase-dUTP nick-end labeling assay. Evidence of vector-specific sequences were determined using reverse-transcriptase polymerase chain reaction. Vector dissemination and biodistribution was monitored using a series of assays (cytopathic effects assay, Ad5 hexon enzyme-linked immunosorbent assay, vector-specific polymerase chain reaction assay, and antibody response assay). RESULTS: Twenty-four patients (median age, 64 years) received a total of 83 intratumor injections with Adp53. The maximum dose administered was 1 x 10(11) PFU per dose. Transient fever related to Adp53 injection developed in eight of 24 patients. Seventeen patients achieved a best clinical response of stable disease, two patients achieved a partial response, four patients had progressive disease, and one patient was not assessable. A mean apoptotic index between baseline and follow-up measurements increased from 0.010 to 0.044 (P =.011). Intratumor transgene mRNA was identified in 43% of assessable patients. CONCLUSION: Intratumoral injection with Adp53 in combination with cisplatin is well tolerated, and there is evidence of clinical activity.

Adenoviruses, Human↗

PubMed1999

Induction chemotherapy employing dose-intense cisplatin with mitomycin and vinblastine (MVP400), followed by thoracic surgery or irradiation, for patients with stage III nonsmall cell lung carcinoma.

BACKGROUND: Cisplatin-based induction chemotherapy before surgery or irradiation has improved the survival of patients with Stage III nonsmall cell lung carcinoma (NSCLC). Encouraged by earlier results with preoperative MVP (cisplatin [120 mg/m(2) or 25 mg/m(2)/week], vinblastine, and mitomycin) for Stage IIIA patients with clinically apparent mediastinal (N2) disease, the authors conducted a Phase II trial of the safety and efficacy of induction MVP400 with the dose intensity of cisplatin doubled from 25 to 50 mg/m(2) per week. METHODS: From October 1992 to March 1996, 37 patients with Stage IIIA (26) or Stage IIIB (11) NSCLC began the MVP400 induction chemotherapy program. Four doses of cisplatin (100 mg/m(2)), 7 doses of vinblastine, and 2 doses of mitomycin were given over 9 weeks. Patients received either surgery or irradiation after induction treatment. RESULTS: Overall, the response rate was 65% (95% confidence interval, 49-81%) with a complete resection rate of 67%. The median survival was 17 months, with 66% of patients alive at 1 year. Complete resection and Stage IIIA involvement were favorable prognostic indicators for survival. No Stage IIIB patients underwent a complete resection. Myelosuppression was the most common side effect. There were no treatment-related deaths. CONCLUSIONS: Although high response and complete resection rates were again demonstrated, results with the MVP400 regimen were not improved over those achieved with MVP regimen tested earlier with Stage IIIA (N2) patients. The authors continue to recommend MVP as an induction chemotherapy regimen for clinical trials.

Adult↗

PubMed1999

Adenovirus-mediated p53 gene transfer in advanced non-small-cell lung cancer.

BACKGROUND: Preclinical studies in animal models have demonstrated tumor regression following intratumoral administration of an adenovirus vector containing wild-type p53 complementary DNA (Ad-p53). Therefore, in a phase I clinical trial, we administered Ad-p53 to 28 patients with non-small-cell lung cancer (NSCLC) whose cancers had progressed on conventional treatments. METHODS: Patients received up to six, monthly intratumoral injections of Ad-p53 by use of computed tomography-guided percutaneous fine-needle injection (23 patients) or bronchoscopy (five patients). The doses ranged from 10(6) plaque-forming units (PFU) to 10(11) PFU. RESULTS: Polymerase chain reaction (PCR) analysis showed the presence of adenovirus vector DNA in 18 (86%) of 21 patients with evaluable posttreatment biopsy specimens; vector-specific p53 messenger RNA was detected by means of reverse transcription-PCR analysis in 12 (46%) of 26 patients. Apoptosis (programmed cell death) was demonstrated by increased terminal deoxynucleotide transferase-mediated biotin uridine triphosphate nick-end labeling (TUNEL) staining in posttreatment biopsy specimens from 11 patients. Vector-related toxicity was minimal (National Cancer Institute's Common Toxicity Criteria: grade 3 = one patient; grade 4 = no patients) in 84 courses of treatment, despite repeated injections (up to six) in 23 patients. Therapeutic activity in 25 evaluable patients included partial responses in two patients (8%) and disease stabilization (range, 2-14 months) in 16 patients (64%); the remaining seven patients (28%) exhibited disease progression. CONCLUSIONS: Repeated intratumoral injections of Ad-p53 appear to be well tolerated, result in transgene expression of wild-type p53, and seem to mediate antitumor activity in a subset of patients with advanced NSCLC.

Adenoviridae↗

PubMed1999

Oral cisapride for the control of delayed vomiting following high-dose cisplatin.

Although combination antiemetics prevent vomiting during the initial 24 h after high-dose (> or =100 mg/m2) cisplatin, many patients experience delayed emesis 24-120 h afterwards despite receiving prophylactic dexamethasone and metoclopramide during this time. Cisapride is a prokinetic agent, which stimulates propulsive motility throughout the gastrointestinal tract without causing extrapyramidal effects. In this phase II trial, we tested the ability of cisapride to prevent delayed emesis following cisplatin. Twenty patients receiving initial cisplatin >100 mg/m2 were entered. All patients received intravenous dexamethasone with either metoclopramide or ondansetron to prevent acute emesis 0-24 h after receiving cisplatin. Patients who had experienced two or fewer acute vomiting episodes then received cisapride 20 mg orally four times daily for 4 days (24-120 h after cisplatin). Cisapride prevented delayed emesis in 2 patients (10%) during the entire 4-day period (95% confidence interval, 1-32%). Abdominal cramping and pain occurred in 35%. At the dose and schedule tested, oral cisapride prevented delayed emesis in only 10% of patients receiving cisplatin >100 mg/m2 and caused abdominal cramping in 35%. Since in prior trials among similar patients, placebo prevented delayed emesis in 11%, further study of cisapride and dose escalation for this indication are not recommended.

Abdominal Pain↗

PubMed1999

Phase I study of the sequential administration of edatrexate and paclitaxel in patients with advanced solid tumors.

BACKGROUND: The antifolate edatrexate and the microtubule-stabilizing agent paclitaxel have both demonstrated single-agent activity in lung and breast cancer. In vitro, the sequential combination of edatrexate followed by paclitaxel produced synergistic antitumor effects. This trial was designed to find the maximum tolerated doses of edatrexate and paclitaxel when given every two weeks utilizing this sequential schedule. PATIENTS AND METHODS: Thirty-four patients with solid tumors received edatrexate intravenously on days 1 and 15 and paclitaxel intravenously as a three-hour infusion on days 2 and 16 of each 28-day cycle. Edatrexate was escalated from 40 to 120 mg/m2 and the paclitaxel dose fixed at 135 mg/m2. When the maximum-tolerated dose was not reached, edatrexate was fixed at 120 mg/m2 and paclitaxel escalated to 175 and 210 mg/m2. RESULTS: All 34 patients were assessable. The maximum tolerated doses were 120 mg/m2 of edatrexate and 210 mg/m2 of paclitaxel. Grade 3 myalgia, peripheral neuropathy, leukopenia, and an infusion-related reaction occurred. Eight patients with non-small-cell lung cancer and one with bladder cancer achieved major objective responses. CONCLUSIONS: The recommended phase II doses are 120 mg/m2 of edatrexate days 1 and 15 and 175 mg/m2 of paclitaxel as a three-hour infusion days 2 and 16 of a 28 day cycle. These results warrant phase II trials of the combination leading to phase III studies comparing the two drugs to a single agent to confirm the preclinical evidence of synergy.

Adult↗

PubMed1999

Cisplatin, etoposide, and paclitaxel in the treatment of patients with extensive small-cell lung carcinoma.

PURPOSE: The combination of cisplatin, etoposide, and paclitaxel was studied in patients with extensive small-cell lung cancer in a phase I component followed by a phase II trial to determine the maximum-tolerated dose (MTD), characterize toxicity, and estimate response and median survival rates. PATIENTS AND METHODS: Forty-one patients were treated between October 1993 and April 1997. Doses for the initial cohort were cisplatin 75 mg/m(2) on day 1, etoposide 80 mg/m(2)/d on days 1 to 3, and paclitaxel 130 mg/m(2) on day 1 over 3 hours. Cycles were repeated every 3 weeks for up to six cycles. The MTD was reached in the first six patients. In these six patients and in the next 35 patients, who were entered onto the phase II trial, response and survival were estimated. RESULTS: At the initial dose level, one of six patients developed febrile neutropenia, and five of six achieved targeted neutropenia (nadir absolute granulocyte count, 100 to 1,000/microL) without any other dose-limiting toxicity, defining this level as the MTD. Grade 4 neutropenia was observed in 88 (47%) of 188 total courses administered at or less than the MTD. Neutropenia was associated with fever in only 17 (9%) of 188 courses, but two patients experienced neutropenic sepsis that was fatal. Nonhematologic toxicity greater than grade 2 was observed in 10 (5%) of 188 total courses, with fatigue, peripheral neuropathy, and nausea/vomiting most common. The overall objective response rate was 90% of 38 assessable patients: six complete responses (16%) and 28 partial responses(74%). Median progression-free and overall survival durations were 31 and 47 weeks, respectively. CONCLUSION: The combination of cisplatin, etoposide, and paclitaxel produced response and survival rates similar to those of other combinations and was well tolerated.

Adult↗

PubMed1998

A multidisciplinary approach to therapy for unresectable malignant thymoma.

BACKGROUND: The therapeutic outcome for unresectable, locally advanced, malignant thymoma has been poor. OBJECTIVE: To improve tumor resectability and patient survival rates by studying a multimodal approach to therapy for unresectable malignant thymoma. DESIGN: Prospective cohort study. SETTING: Tertiary care cancer center. PARTICIPANTS: All eligible patients had newly diagnosed, histologically proven, unresectable malignant thymoma. INTERVENTION: The treatment regimen consisted of induction chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone), surgical resection, postoperative radiation therapy, and consolidation chemotherapy (three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone). Tissue samples were taken at the time of surgical resection for assessment of tumor necrosis and Ki-67 expression. MEASUREMENTS: Tumor response and resectability (both overall and after induction chemotherapy) and disease-free survival rate in patients who received multimodal therapy. RESULTS: 13 patients were consecutively enrolled from February 1990 to December 1996, and 12 evaluable patients were assessed for response. Disease responded to induction chemotherapy completely in 3 patients (25%) and partially in 8 patients (67%); 1 patient had a minor response (8%). Eleven patients had surgical resection; 1 refused surgery. Tumors were removed completely in 9 (82%) and incompletely in 2 (18%) of 11 patients who had been receiving radiation therapy and consolidation chemotherapy. All 12 patients are alive (100% at 7 years), with a median follow-up of 43 months, and 10 patients are disease free (73% disease-free survival at 7 years). A high correlation was seen between tumor necrosis after induction chemotherapy and Ki-67 expression (r=-0.88). CONCLUSIONS: Aggressive multimodal treatment is highly effective and may cure locally advanced, unresectable malignant thymoma.

Adult↗

PubMed1998

Phase II study of intravenous adenosine 5'-triphosphate in patients with previously untreated stage IIIB and stage IV non-small cell lung cancer.

Fifteen patients with Stage IIIB or IV non-small cell lung cancer gave informed consent to receive three or more 96-hour infusions of ATP at a dose of 50 mcg/kg/min or higher to determine whether ATP has antineoplastic activity against this tumor type and to better define the spectrum of toxicity for ATP given as a single agent. There were no objective complete or partial responses observed. The median survival of the overall group was 187 days and the median time to tumor progression was 113 days. The major toxic side effects were chest pain and dyspnea, leading to the cessation of treatment in 5 patients. We conclude that ATP at this dose and schedule of administration is an inactive agent in patients with advanced non-small cell lung cancer.

Adenosine Triphosphate↗

PubMed1997

Phase II trial of chloroquinoxaline sulfonamide (CQS) in patients with stage III and IV non-small-cell lung cancer.

PURPOSE: Chloroquinoxaline sulfonamide (CQS) was one of the first agents identified by the human tumor colony-forming assay (HTCFA) as possessing antitumor activity in non-small-cell lung cancer (NSCLC). Prior phase I studies had suggested that plasma concentrations equivalent to those showing efficacy in the HTCFA could be reliably attained in humans. This phase II study assessed the antitumor activity of CQS while using an adaptive control pharmacokinetic modelling system to attain targeted plasma levels of this novel compound. METHODS: A group of 20 patients with stage III or IV NSCLC received CQS as a 1-h weekly infusion at an initial dose of 2 g/m2. In all patients, 24-h plasma concentrations of CQS were measured. Patients with levels < 100 micrograms/ml had dose increases determined by their 24-h levels and pharmacokinetic parameters obtained from two prior phase I trials of this agent. These individuals had 24-h CQS levels repeated after their second weeks' treatment and doses were readjusted if the target concentration was not reached. Antitumor response assessment was made every 6 weeks. RESULTS: Of the 20 patients, 18 attained the target plasma concentration, and 16 of these achieved this initially or with just one dose adjustment. No major objective antitumor responses were observed (major response rate 0%, 95% CI 0-17%). CQS was well tolerated with hypoglycemia being the most clinically significant toxicity. CONCLUSIONS: When given on this schedule CQS is inactive in NSCLC despite the fact that the target concentration was achieved in 90% of patients. The ability of the HTCFA to identify active agents remains unproved.

Adult↗