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Biomedical subjects

F Shepherd

Publications and source records attributed to F Shepherd.

At least 19 recordsLinked to original sources
PubMed2004

Randomized phase II trial of gemcitabine-cisplatin with or without trastuzumab in HER2-positive non-small-cell lung cancer.

BACKGROUND: Trastuzumab provides significant clinical benefits in HER2-positive metastatic breast cancer patients when administered in combination with chemotherapy. Chemotherapy has also been shown to be beneficial in some patients with advanced non-small-cell lung cancer (NSCLC). The present randomized phase II trial examined the effect of adding trastuzumab to a standard chemotherapeutic combination (gemcitabine-cisplatin) in patients with HER2-positive NSCLC. PATIENTS AND METHODS: Patients with untreated stage IIIB/IV HER2-positive NSCLC received up to six 21-day cycles of gemcitabine 1250 mg/m(2) (days 1 and 8) and cisplatin 75 mg/m(2) (day 1). Patients in the trastuzumab arm received trastuzumab 4 mg/kg intravenously (i.v.) followed by 2 mg/kg/week i.v. until progression. RESULTS: Of 619 patients screened, 103 were eligible. Fifty-one patients were treated with trastuzumab plus gemcitabine-cisplatin and 50 with gemcitabine-cisplatin alone. Efficacy was similar in the trastuzumab and control arms: response rate 36% versus 41%; median time to progression 6.3 versus 7.2 months; and median progression-free survival (PFS) 6.1 versus 7 months. Response rate (83%) and median PFS (8.5 months) appeared relatively good in the six trastuzumab-treated patients with HER2 3+ or fluorescence in situ hybridization (FISH)-positive NSCLC. Addition of trastuzumab to gemcitabine-cisplatin was well tolerated, side-effects were as expected, and trastuzumab did not exacerbate the known toxicity of gemcitabine and cisplatin. Symptomatic cardiotoxicity was observed in one trastuzumab-treated patient. Serum trastuzumab concentrations in the presence of gemcitabine-cisplatin were comparable to those of trastuzumab alone. CONCLUSIONS: Trastuzumab plus gemcitabine-cisplatin is well tolerated. Clinical benefit was not observed. Although HER2 3+/FISH-positive patients may benefit from trastuzumab, the subgroup is too small to provide definitive information. No significant effect of gemcitabine-cisplatin on trastuzumab pharmacokinetics was observed.

Adult↗
PubMed2003

The PIVKA II test: the first reliable coagulation test for autopsy investigations.

To date there is no routinely used reliable diagnostic test that can be performed in the post-mortem period to investigate whether a deceased had a coagulation disorder. This paper describes a series of experiments to assess the use of an antigen-based method to investigate the vitamin K-dependent factor II function in the deceased. It illustrates that by using this approach the functional status of factor II can be investigated in the post-mortem period. The abnormal proteins that are investigated by this method appear to remain stable for at least 72 h and potentially up to at least 7 days. The method that is illustrated could thus be reliably used in the post-mortem period to identify a natural or drug-induced factor II abnormality. The potential for other protein components of the coagulation cascade to be investigated by similar antigen-based methodology is suggested.

Aged↗
PubMed2001

Molecular cytogenetic analysis of non-small cell lung carcinoma by spectral karyotyping and comparative genomic hybridization.

The overall pattern of chromosomal changes detected by spectral karyotype (SKY) analysis of two cell lines of each major histological subtype of NSCLC, namely squamous cell carcinoma (SQCC) and adenocarcinoma (ADC), indicated a greater degree of chromosomal rearrangement, than was present or predicted by either comparative genomic hybridization (CGH) or G-banding analysis alone. To investigate these observations, CGH was used to screen DNA derived from 8 primary tumors and 15 cell lines. The results indicated that the most frequently gained chromosome arms were 5p (70%), 8q (65%), 15q (52%), 20q (48%), 1q (43%), 19q (39%), 3q (35%), and 11q (35%). Chromosomal losses were less frequently observed, and included 18q (39%), 9 (35%), 6q (30%), 13q (21%), 5q12-q32 (17%), and 19p (17%). Amplifications were found on 2p23-p24, 3q24-q27, 5p, 6cen-p21.1, 6q26, 7p21, 7q31, 8q, 11q13-qter, 20q12-q13.2. Comparison between CGH findings of the two major histological subtypes showed that gains at 1q22-q32.2, 15q, 20q, and losses at 6q, 13q, and 18q was common in ADCs, whereas SQCCs exhibited gains/amplifications at 3q. Distal 8q was gained by CGH in 65% of tumors of both subtypes. Low level MYCC amplification was confirmed by direct fluorescence in situ hybridization (FISH) analysis. The pattern of overall chromosomal changes detected using combinations of molecular cytogenetic analytical methods suggests that it will be easier to detect recurrent subtype-dependent aberrations in NSCLC.

Adenocarcinoma↗
PubMed2001

Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: Initial results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160).

OBJECTIVE: The rate of complete resection (50%) and the 5-year survival (30%) for non-small cell lung carcinomas of the superior sulcus have not changed for 40 years. Recently, combined modality therapy has improved outcome in other subsets of locally advanced non-small cell lung carcinoma. This trial tested the feasibility of induction chemoradiation and surgical resection in non-small cell lung carcinoma of the superior sulcus with the ultimate aim of improving resectability and survival. METHODS: Patients with mediastinoscopy-negative T3-4 N0-1 superior sulcus non-small cell lung carcinoma received 2 cycles of cisplatin and etoposide chemotherapy concurrent with 45 Gy of radiation. Patients with stable or responding disease underwent thoracotomy 3 to 5 weeks later. All patients received 2 more cycles of chemotherapy and were followed up by serial radiographs and scans. Survival was calculated by the Kaplan-Meier method and prognostic factors were assessed for significance by Cox regression analysis. RESULTS: From April 1995 to September 1999, 111 eligible patients (77 men, 34 women) were entered in the study, including 80 (72.1%) with T3 and 31 with T4 tumors. Induction therapy was completed as planned in 102 (92%) patients. There were 3 treatment-related deaths (2.7%). Cytopenia was the main grade 3 to 4 toxicity. Of 95 patients eligible for surgery, 83 underwent thoracotomy, 2 (2.4%) died postoperatively, and 76 (92%) had a complete resection. Fifty-four (65%) thoracotomy specimens showed either a pathologic complete response or minimal microscopic disease. The 2-year survival was 55% for all eligible patients and 70% for patients who had a complete resection. To date, survival is not significantly influenced by patient sex, T status, or pathologic response. CONCLUSIONS: (1) This combined modality treatment is feasible in a multi-institutional setting; (2) the pathologic complete response rates were high; and (3) resectability and overall survival were improved compared with historical experience, especially for T4 tumors, which usually have a grim prognosis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

No association between hepatitis C and B-cell lymphoma.

Chronic viral infection has been implicated in the pathogenesis of B-cell lymphoma, and hepatitis C virus (HCV) infects lymphocytes. Chronic infection with HCV may result in B-cell proliferation. Individuals infected with hepatitis C are often co-infected with the RNA virus GB virus type C. Studies from Europe where hepatitis C infection is more common than in North America have shown a high prevalence of hepatitis C infection in patients with B-cell lymphoma. The aim of this study was to establish the prevalence of HCV and GBV-C infection in patients with B-cell lymphoma in an area of low HCV prevalence. One hundred patients with B-cell lymphoma (10 high grade, 46 intermediate grade, and 44 low grade) and 100 controls with nonhematological malignancies were studied. Serum was analyzed for HCV antibodies by third generation enzyme-linked immunosorbant assay, and HCV RNA and GBV-C RNA was analyzed by reverse transcriptase PCR. None of the controls or lymphoma patients had antibodies to HCV. HCV RNA was undetected in 60 out of 100 lymphoma patients tested. GBV-C RNA was detected in the serum of 5 out of 100 (5%) of lymphoma patients and in 3 out of 100 (3%) controls. Hepatitis C and GBV-C are, therefore, unlikely to play a major role in the pathogenesis of B-cell lymphoma in North America.

Antibodies, Viral↗
PubMed1999

Phase I trial of sequential topotecan followed by etoposide in adults with myeloid leukemia: a National Cancer Institute of Canada Clinical Trials Group Study.

Prolonged exposure to a topoisomerase I inhibitor may increase expression of topoisomerase II, making cells more susceptible inhibitors of that enzyme. This study was undertaken to establish the maximum tolerated dose (MTD) of a topotecan/topoisomerase II inhibitor sequential combination that may be active in acute leukemia, and to evaluate the effects of in vivo exposure to topotecan on topoisomerase II levels in leukemic blast cells as measured by image cytometry. Patients who were eligible for this phase I study had relapsed or refractory acute myeloid leukemia (< or = 2 prior regimens) or CML blast crisis (0 or 1 prior regimen). Topotecan was given as a 5 day continuous i.v. infusion and was to be escalated through three levels (1.5, 1.75 and 2.0 mg/m2 day), followed by etoposide at two dose levels (100 and 150 mg/m2) i.v. bolus days 6, 7 and 8. Topoisomerase IIalpha levels in leukemic blasts from bone marrow were measured by image cytometry prior to starting treatment, on day 5 of topotecan infusion and on day 28; and daily during topotecan in peripheral blood blasts. Dose-limiting toxicity was seen in two of six patients at the first dose level (topotecan 1.5 mg/m2/day, etoposide 100 mg/m2/day; > or = grade 3 mucositis in both cases). This cohort was expanded to 10 patients; no further non-hematologic dose-limiting toxicity was observed, but given the extent of toxicity seen, further dose escalation was judged not to be feasible. Topo IIalpha levels increased in peripheral blood blasts during the first 72 h of topotecan infusion and returned to near baseline by day 5, whereas levels appeared to decrease in bone marrow blasts by day 5 compared to pretreatment. One complete hematologic and cytogenetic remission in a patient with CML blast crisis was observed in the 10 patients evaluable for response. The sequential administration of topotecan 1.5 mg/m2/day continuous infusion for 5 days followed by etoposide 100 mg/m2/day x 3 is the recommended phase II dose for this schedule. Topotecan increases topo IIalpha expression in vivo in leukemia cells, but levels of the enzyme are cell cycle dependent. Pharmacodynamic evaluation of the sequential or combination administration of novel antileukemic agents may help improve treatment strategies in acute leukemia.

Acute Disease↗
PubMed1998

Use of dexamethasone and granisetron in the control of delayed emesis for patients who receive highly emetogenic chemotherapy. National Cancer Institute of Canada Clinical Trials Group.

PURPOSE: To evaluate the roles of granisetron and dexamethasone for emesis control on days 2 through 7 after the administration of cisplatin in doses of 50 mg/m2 or greater to patients who had not previously received chemotherapy. PATIENTS AND METHODS: Four hundred thirty-five eligible and assessable patients were randomized to one of two arms in a double-blind fashion: arm A; granisetron 3 mg intravenous (i.v.) plus dexamethasone 10 mg i.v. prechemotherapy followed by granisetron 1 mg orally at 6 and 12 hours, then granisetron 1 mg orally and dexamethasone 8 mg orally twice daily on days 2 through 7 (219 patients); arm B; as in arm A but with placebo substituted for granisetron on days 2 through 7 (216 patients). All patients completed diaries in which episodes of emesis and severity of nausea were recorded. RESULTS: The addition of granisetron on days 2 through 7 had no discernable impact on nausea and vomiting during this period. CONCLUSION: The administration of a 5-hydroxytryptamine3, receptor (5-HT3) antagonist, in this case granisetron, after 24 hours conferred no benefit. This negative result needs to be assessed in light of conflicting literature, but at present it does not appear that the routine use of these drugs in this setting is justified.

Antiemetics↗
PubMed1997

Primary bilateral adrenal lymphoma.

We report a case of primary bilateral adrenal non-Hodgkins lymphoma (NHL), with hypercalcemia at the time of presentation. Medical literature review showed that this is an extremely rare site for lymphoma, but presents a distinct clinical entity with many features that differ from NHL overall, extranodal NHL, and NHL in other endocrine organs. The diagnosis is frequently not suspected antemortem, and long delays between the onset of symptoms and the diagnosis are frequent. Adrenal insufficiency is also common, and may be a lethal complication of these tumors. Response to therapy and survival are extremely poor.

Adrenal Gland Neoplasms↗
PubMed1997

[A phase II multicenter study of gemcitabine in non small cell lung cancers].

Gemcitabine is a novel pyrimidine nucleoside whose activity has been demonstrated on solid tumors. We report here the results of a multicentre phase II trial of gemcitabine in chemonaive patients with inoperable non small cell lung cancer (NSCLC). Gemcitabine was given weekly at a dose of 1,250 mg/m2 administered as a 30 min intravenous infusion, for 3 weeks followed by 1 week of rest (1 cycle). All the 161 patients included were evaluable for toxicity and 151 of them were evaluable for efficacy. The majority of patients had a stage IIIb (31.1%) or stage IV (64.6%) disease; 10.6%, 83.2% and 6.2% of patients had a WHO performance status (PS) 0, 1, and 2, respectively. Adenocarcinoma accounted for 52.2% of cases and squamous cell carcinoma for 43.5% of cases. Three complete responses and 30 partial responses gave an objective response (OR) rate of 21.8% (95% confidence interval; 15.5-29.3%). All responses were validated by an independent Oncology Review Board. Median duration of response was 7.6 months. Median time to progression was 4.6 months (3.3 months in non responders and 7.6 months in responders). Median survival was 7.3 months in non responders and 13.4 months in responders (p < 0.001), which gave an overall median survival of 8.9 months (95% CI: 0.1-21.9 months) in the entire study population. An improvement of symptoms and personal state was also observed. Treatment was well tolerated. Neutropenia was the only dose limiting toxicity. WHO grade 3 or 4 neutropenia occurred in 19.6% and 5.7% of patients, respectively. With a 21.8% OR rate, this multicentre study confirms the activity of gemcitabine as a single agent in patients with inoperable NSCLC. Its good tolerance and original mode of action make gemcitabine a drug of choice in the therapeutic strategy of these tumors.

Adult↗
PubMed1997

Angiogenesis correlates with vascular endothelial growth factor expression but not with Ki-ras oncogene activation in non-small cell lung carcinoma.

A total of 195 non-small cell lung carcinoma (NSCLC) specimens were studied for the presence of mutations in their ras family genes, for tumor vascularity, and for their immunostaining pattern with an antibody to vascular endothelial growth factor (VEGF). ras mutation was found in 37 of 104 (34.6%) adenocarcinoma specimens, in 0 of 64 squamous cell carcinomas, and in 2 of 27 (7.4%) large cell undifferentiated carcinomas. All mutations were found on the Ki-ras gene, with 37 (95%) of them on codon 12 and the remaining 2 on codon 13. Thirty (77%) of the mutations were G to T transversions. There was a correlation between increasing tumor vascularity and VEGF immunostaining score, but there was no correlation between either of them with the activation of the ras oncogene. A study of VEGF mRNA expression in 14 NSCLC cell lines also demonstrated a lack of correlation between the constitutive expression levels of VEGF and the presence or absence of ras mutation in these cell lines. The results suggest that VEGF is a major angiogenesis factor in NSCLC but that other factors beside ras mutations may influence tumor vascularity in these tumors. The two parameters may potentially serve as independent prognostic factors in NSCLC.

Alleles↗
PubMed1996

Tallimustine is inactive in patients with previously treated small cell lung cancer. A phase II trial of the National Cancer Institute of Canada Clinical Trials Group.

Tallimustine binds to the minor groove of DNA where it alkylates the N3 position of adenine and may interfere with gene transcription. We conducted a phase II trial of Tallimustine given at a dose of 750 micrograms/m2 intravenously every 4 weeks in patients with small cell lung cancer progressing or relapsing following cisplatin or carboplatin-based chemotherapy. We treated 14 eligible patients with a performance status 0, 1 or 2, bi-dimensionally measurable disease and adequate end-organ function. The main toxicity was neutropenia with a median granulocyte count of 0.1 x 10(9) per liter (range 0-3.9) and four patients (27%) developing febrile neutropenia. In addition, most patients (93%) experienced lethargy. No objective responses were seen. A mixed response was seen in one patient and three others had stable disease for a median of 3.7 months. We conclude that Tallimustine is an ineffective agent in previously treated small cell lung cancer.

Aged↗
PubMed1996

Randomized phase III trial of liposomal daunorubicin versus doxorubicin, bleomycin, and vincristine in AIDS-related Kaposi's sarcoma.

PURPOSE: To compare the safety and efficacy of liposomal daunorubicin (DaunoXome; NeXstar Pharmaceuticals, Inc, Boulder, CO) with a reference regimen of doxorubicin, bleomycin, and vincristine (ABV) in advanced AIDS-related Kaposi's sarcoma (KS). PATIENTS AND METHODS: In a prospective randomized phase III trial, 232 patients were randomized to receive DaunoXome 40 mg/m2 or a combination regimen of doxorubicin 10 mg/m2, bleomycin 15 U, and vincristine 1 mg, administered intravenously every 2 weeks. Treatment was continued until complete response (CR), disease progression, or unacceptable toxicity. RESULTS: Of 232 patients randomized, 227 were treated: 116 with DaunoXome and 111 with ABV. The overall response rate (CR or partial response [PR]) was 25% (three CRs and 26 PRs) for DaunoXome and 28% (one CR and 30 PRs) for ABV. The difference in response rates was not statistically significant. The median survival time was 369 days for DaunoXome patients and 342 days for ABV patients (P = .19). The median time to treatment failure was 115 days for DaunoXome and 99 days for ABV (P = .13). ABV patients experienced significantly more alopecia and neuropathy (P < .0001). DaunoXome patients experienced more grade 4 neutropenia (P = .021). Cardiac function remained stable, with no instances of congestive heart failure on either treatment arm. CONCLUSION: In this large phase III trial, the efficacy of DaunoXome was comparable to that of ABV. Response rates, time to treatment failure, and overall survival were similar on both treatment arms. DaunoXome is a safe and effective primary therapy for advanced AIDS-related KS.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Dexamethasone improves the efficacy of granisetron in the first 24 h following high-dose cisplatin chemotherapy.

The object of the study was to determine whether dexamethasone improved the efficacy of the serotonin receptor (5-HT3) antagonist granisetron in controlling acute (within 24 h) emesis in cancer patients receiving high-dose cisplatin chemotherapy and to ascertain whether continuation of granisetron after 24 h reduces the occurrence of delayed emesis. This randomised, double-blind, multicentre, three-arm study was conducted at 21 medical centres. A group of 292 nausea- and emesis-free patients with cancer, who had never had chemotherapy and were scheduled to receive at least 50 mg/m2 cisplatin, were given 3 mg granisetron i.v. in a 15-min infusion with or without 10 mg dexamethasone i.v. completed 5 min prior to high-dose cisplatin and 1 mg granisetron p.o. at +6 h and +12 h. Primary study end-points were control of emesis and nausea. Patients completed a self-report diary every 6 h for the first 24 h. At the end of the 24-h period, the patients who received dexamethasone had a significantly higher complete protection rate from emesis (64% compared to 39%) than those who received no steroid. Similarly, the dexamethasone-treated group had a significantly higher complete plus partial (0-2 emetic episodes) protection rate (84% compared to 64%). This study shows that dexamethasone markedly enhances the antiemetic efficacy of granisetron for acute-onset emesis in high-dose cisplatin chemotherapy.

Acute Disease↗
PubMed1995

DICE (dexamethasone, ifosfamide, cisplatin, etoposide) as salvage therapy in non-Hodgkin's lymphomas.

Between April 1988 and April 1992 we conducted a study of DICE (dexamethasone 10 mg q6h, ifosfamide 1 g/m2, cisplatin 25 mg/m2, etoposide 100 mg/m2, and mesna uroprotection daily x 4 given every 28 days) in thirty six patients with intermediate or high-grade non-Hodgkin's lymphomas (NHL's). All patients had disease refractory to anthracycline-based chemotherapy and were ineligible for our dose intensive salvage chemotherapy program including autologous bone marrow transplant (ABMT). Twenty six men and 10 women aged 21-79 years (median 61) were given 100 courses of treatment in hospital. Twenty three patients had stage IV, 7 stage III and 6 stage II disease. Fourteen patients had bone marrow involvement and 11 had B symptoms. Thirty two patients had received only 1 previous chemotherapy regimen. After a follow-up of 1-70 months (median 7), 8 of the 34 (23%) patients evaluable for response had complete remission (CR) of their disease for 8-70+ months (med 24) and 15/34 (44%) partial remission (PR) for 2-55+ months (med 13), giving an overall response rate of 67% (23/34). Eight of the 36 patients are alive 34-70 months (median 48) after being enrolled on study, 6 of whom relapsed and responded to subsequent treatment. The estimated survival rates for all patients at 1 and 2 years are 50% and 36% respectively (Kaplan Meier). Response to prior chemotherapy was the only baseline characteristic statistically predictive (p = 0.04) of response to DICE by logistic regression analysis. Myelosuppression was the dose limiting toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Phase II study of elsamitrucin in non-small cell lung cancer.

Elsamitrucin (BMY-28090) a novel fermentation product has demonstrated pre-clinical anti-tumour activity against a number of cell lines. The dose limiting toxicity in phase I studies was a reversible increase in hepatic transaminase. This study was initiated to determine the activity of elsamitrucin in patients with previously untreated, bi-dimensionally measurable, cytologically or histologically proven, non-small cell lung cancer who were not curable by surgery. Elsamitrucin at a dose of 25 mg/m2 was administered intravenously over 5-10 min weekly for a minimum of 6 weeks. Seventeen patients were entered on study, 15 were evaluable for toxicity and 14 evaluable for response. No responses were documented in the 14 patients evaluable for response. Both hematological and non-hematological toxicities were mild to moderate in severity. The commonest being nausea, vomiting, lethargy and local skin reactions at the site of the infusion. These results indicate that elsamitrucin when given in this dose and schedule to patients with surgically incurable non-small cell lung cancer has no activity.

Aged↗
PubMed1994

Dose-ranging study of recombinant human granulocyte-macrophage colony-stimulating factor in small-cell lung carcinoma.

PURPOSE: This randomized, multicenter, dose-finding study was undertaken to determine the dose of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) that can safely reduce neutropenia after cyclophosphamide, doxorubicin, and etoposide (CAVP-16) chemotherapy in patients with small-cell lung cancer (SCLC). Secondary clinical end points included incidence of infection, intravenous (IV) antimicrobial use, and chemotherapy delivered. PATIENTS AND METHODS: A total of 290 newly diagnosed SCLC patients were to receive six cycles of standard CAVP-16 chemotherapy on days 1 to 3 of every 21 days alone or with rhGM-CSF at 5, 10, or 20 micrograms/kg, administered subcutaneously (SC) on days 4 to 13 of each cycle. RESULTS: In cycle 1, median absolute neutrophil count (ANC) nadirs were twofold to threefold higher in patients who received rhGM-CSF, although all values were less than 500/microliters, and recovery from neutropenia was faster at all rhGM-CSF dosages versus observation (P < or = .01). In cycle 2, 56% of all patients given rhGM-CSF received full chemotherapy dosages (87.5% to 112.5% of projected dose) versus 36% of observation patients. During days 5 to 21 of cycle 1, fewer patients who received 10 micrograms/kg of rhGM-CSF required antibiotics compared with observation patients (11% v 29%, P < or = .01). Adverse events that occurred more frequently in rhGM-CSF-treated patients included injection-site reaction, edema, asthenia, paresthesia, diarrhea, myalgia, musculoskeletal pain, Pruritus, and rash (P < or = .10). Fever occurred more frequently in the 10- and 20-micrograms/kg rhGM-CSF groups than in the observation groups. The incidence in the 5-microgram/kg group was comparable to that in observation patients. Patients who received rhGM-CSF had a higher incidence of thrombocytopenia. CONCLUSION: rhGM-CSF at 5 to 10 micrograms/kg reduces chemotherapy-associated neutropenia and should be the dose range used in future studies.

Adult↗
PubMed1994

Vinorelbine (Navelbine) in the adjuvant and neoadjuvant treatment of non-small cell lung cancer.

Several Canadian centers are studying the favorable activity and toxicity profile of vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) in current and future trials of adjuvant and neoadjuvant treatment of non-small cell lung cancer. In locally advanced, unresectable disease, the 10-week regimen in cisplatin 100 mg/m2 during weeks 1 and 5, vinorelbine 30 mg/m2 weekly for 5 weeks with a 50% dose reduction planned for week 2 only, and accelerated fractionation thoracic irradiation during weeks 7 to 10 (30 fractions of 2 Gy in 4 weeks, once daily during weeks 7 and 8, and twice daily during weeks 9 and 10). Preliminary data on 17 patients who have completed treatment to date show it has been well tolerated, with only four cases of grade 3 nonhematologic toxicities. Favorable results from combined therapy with cisplatin and vinorelbine in advanced disease have led the National Cancer Institute of Canada Clinical Trials Group to consider testing adjuvant cisplatin and vinorelbine in completely resected non-small cell lung cancer. Surgically staged patients with T2, N0 and T1-2N1 tumors will be stratified according to nodal status and presence or absence of ras oncogene mutations in resected tumor DNA. Patients will be randomized to observation or a 16-week trial of adjuvant chemotherapy with cisplatin 50 mg/m2 days 1 and 8 every 4 weeks during the 16 weeks, and vinorelbine 30 mg/m2 weekly for 16 weeks. All resected tumors will be banked for further correlative studies to identify a clinically meaningful panel of molecular prognostic markers.

Antineoplastic Agents↗