Courses Of Cisplatin-based Chemotherapy Research Articles

Effect of prehydration solution on hearing threshold after chemotherapy in patients with head and neck cancers: a retrospective study.

The study aimed to evaluate the effect of prehydration solution on hearing thresholds after cisplatin chemotherapy. In this retrospective cohort study, we reviewed the data of patients who underwent ≥3 courses of cisplatin-based chemotherapy for locally advanced head and neck cancers at a tertiary referral center (n=64). The dextrose solution (DW) group (n=26) received 2 L of normal saline and 1 L of 5% dextrose. The Hartmann solution (HS) group (n=38) received 2 L of normal saline and 1 L of HS. Hearing data were measured 1 day before starting the first course of chemotherapy, and again 20 days after the first, second, and third courses of chemotherapy. The severity of hearing loss was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE). Thresholds at all frequencies after chemotherapy were greater in the DW group than in the HS group. The increase in thresholds in 1 to 4 kHz after the third course of chemotherapy was greater in the DW group than in the HS group. CTCAE grades after the second and third courses of chemotherapy were greater in the DW group than in the HS group. Logistic regression showed that the odds ratio for CTCAE grade 3 or 4 after the third course of chemotherapy in the DW group was 4.84 on univariate analysis. Prehydration using a solution with salt was associated with a decrease in change in hearing thresholds after cisplatin chemotherapy in patients with head and neck cancers.

Primary Upper Urinary Tract Small Cell Carcinoma: A Case Series and Literature Review

Background: Primary upper urinary tract small cell carcinoma (SCC) is exceedingly rare with < 30 cases reported in the literature. Little is known about the incidence, diagnosis, treatment, and outcomes in these patients. We present a series of three patients with primary upper tract SCC.Case Presentation: Patient 1 is an 89-year-old Caucasian male who presented with hydroureteronephrosis and a mass in the proximal right ureter. Biopsy revealed SCC. Without further intervention, the patient died 2 months after his diagnosis. Patient 2 is a 67-year-old Caucasian female who underwent left laparoscopic nephroureterectomy for primary distal ureteral SCC, pT4N1M0. She developed lymphadenopathy and completed external beam radiation to the pelvis and four courses of cisplatin-based chemotherapy. She died from metastatic disease 7 months after diagnosis. Patient 3 is a 45-year-old female who underwent open right radical nephrectomy, retroperitoneal lymph node dissection, and hepatic metastasectomy for metastatic primary upper tract SCC, pT3N1M1. She underwent two subsequent retroperitoneal debulking procedures for recurrence followed by treatment with octreotide. She developed widespread metastasis and was treated with temozolomide and capecitabine before her death 80 months after diagnosis.Conclusion: This series contributes to the limited knowledge of the management and natural course of primary upper tract SCC. Patient 1 represents the first disease-specific mortality reported in a patient who received no therapy. Patient 3 represents the longest reported survival with metastatic disease, and the first treated with octreotide. The patient was managed with aggressive repeat surgical resection and exhibited 2 years of progression-free survival on octreotide. Emphasis should be placed on aggressive resection of all visible disease combined with the use of multimodal adjuvant chemoradiation for selected patients in this rare disease.

SEOM clinical guidelines for the management of germ cell testicular cancer (2016).

Testicular cancer represents the most common malignancy in males aged 15–34 years and is considered a model of curable neoplasm. Maintaining success, reducing treatment burden, and focusing on survivorship are then key objectives. Inguinal orchiectomy is the first recommended maneuver that has both diagnostic and therapeutic aims. Most patients are diagnosed with stage I disease (confined to the testicle). Close surveillance and selective, short-course adjuvant chemotherapy are accepted alternatives for these cases. In patients with more advanced disease (stages II and III), 3–4 courses of cisplatin-based chemotherapy (according to IGCCCG risk classification) followed by the judicious surgical removal of residual masses represent the cornerstone of therapy. Poor-risk patients and those failing a first-line therapy should be referred to specialized tertiary centers. Paclitaxel-based conventional chemotherapy and high-dose chemotherapy plus autologous hematopoietic support can cure a proportion of patients with relapsing or refractory disease.

Impact of acute kidney injury defined by CTCAE v4.0 during first course of cisplatin-based chemotherapy on treatment outcomes in advanced urothelial cancer patients.

The Kidney Disease: Improving Global Outcomes group (KDIGO) defined acute kidney injury (AKI) as an elevation of serum creatinine (sCR) exceeding 0.3mg/dl within 48h. The widely used adverse events criteria for chemotherapy, Common Toxicity Criteria for Adverse Events Version 4.0 (CTCAE v4.0), also defined AKI as sCR exceeding 0.3mg/dl, but with no provision of a time course. Here, we attempted to clarify the impact of AKI(CTCAE v4.0) during cisplatin-based chemotherapy on clinical outcome of patients with advanced urothelial cancer (UC). This multicenter retrospective study included 230 UC patients who received cisplatin-based chemotherapy. During the first chemotherapy course, AKI(CTCAE v4.0) episodes were observed in 61 patients (26.5%), whereas only four patients (1.5%) experienced AKI(KDIGO) episodes. Both the pretreatment estimated glomerular filtration rate (eGFR) and creatinine clearance by Cockcroft-Gault formula were not efficient predictors for the development of AKI(CTCAE v4.0). AKI(CTCAE v4.0) impacted renal function: at the start of second-course chemotherapy, the average eGFR of the patients with AKI(CTCAE v4.0) was 54.1ml/min/1.73m2, significantly lower than that of patients withoutAKI(CTCAE v4.0) (63.4ml/min/1.73m2). As a result, only 57.4% of patients with AKI(CTCAE v4.0) received the planned treatment at the second course. The survival of the patients who developed AKI(CTCAE v4.0) was significantly worse than that of the patients who did not. The 3-year OSs were 10.3 and 21.4%, respectively (P=0.02). The present study demonstrated that AKI(CTCAE v4.0) during chemotherapy had a negative impact on both the intensity of subsequent chemotherapy and oncological outcomes.

The relationship between Glasgow Prognostic Score and serum tumor markers in patients with advanced non-small cell lung cancer.

BackgroundGlasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non–small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC.MethodsWe included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21–1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted.ResultsMedian levels of CYFRA21–1 were 1.5 ng/ml (0.1–3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7–35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4–89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9–134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (P < 0.05). Similar results were found for median levels of CEA and TPS in healthy controls and NSCLC patients (P < 0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and GPS, CEA and GPS, TPS and GPS. The Spearman’s rank correlation coefficient were 0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival analyses showed GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC.ConclusionsOur results showed GPS were positive correlated with CYFRA21-1, CEA and TPS in patients with advanced NSCLC. However, GPS was more efficient in predicting prognosis of advanced NSCLC than these three single prognosis related tumor markers.

Chemotherapy refractory testicular germ cell tumor is associated with a variant in Armadillo Repeat gene deleted in Velco-Cardio-Facial syndrome (ARVCF)

Introduction: There is evidence that inherited genetic variation affects both testicular germ cell tumor (TGCT) treatment outcome and risks of late-complications arising from cisplatin-based chemotherapy. Using a candidate gene approach, we examined associations of three genes involved in the cisplatin metabolism pathway, GSTP1, COMT, and TPMT, with TGCT outcome and cisplatin-induced neurotoxicity. Materials and Methods: Our study population includes a subset of patients (n = 137) from a genome-wide association study at the University of Pennsylvania that evaluates inherited genetic susceptibility to TGCT. All patients in our study had at least one course of cisplatin-based chemotherapy with at least 1 year of follow-up. A total of 90 markers in GSTP1, COMT, and TPMT and their adjacent genomic regions (±20 kb) were analyzed for associations with refractory TGCT after first course of chemotherapy, progression-free survival (PFS), overall survival (OS), peripheral neuropathy, and ototoxicity. Results: After adjustment for multiple comparisons, one Single nucleotide polymorphism (SNP), rs2073743, in the flanking region (±20 kb) of COMT was associated with refractory TGCT after initial chemotherapy. This SNP lies within the intron region of the Armadillo Repeat gene deleted in Velco-Cardio-Facial syndrome (ARVCF). The G allele of rs2073743 predisposed patients to refractory disease with a relative risk of 2.6 (95% CI 1.1, 6.3; P = 0.03). Assuming recessive inheritance, patients with the GG genotype had 22.7 times higher risk (95% CI 3.3, 155.8; P = 0.04) of developing refractory disease when compared to those with the GC or CC genotypes. We found no association of our candidate genes with peripheral neuropathy, ototoxicity, PFS and OS. Discussion: This is the first study to suggest that germline genetic variants of ARVCF may affect TGCT outcome. The result of this study is hypothesis generating and should be validated in future studies.

Multimodal treatment for stage IVA thymoma: A proposable strategy

A retrospective review of a series of consecutive patients was carried out to evaluate the feasibility and the efficacy of a multimodal treatment in the management of stage IVA thymoma at first diagnosis. From 1998 to 2008, 18 patients affected by stage IVA thymoma underwent neoadjuvant chemotherapy, surgery and subsequent mediastinal radiation therapy. There were 10 males and 8 females, mean age 54.5years (range 29–68). Not specific symptoms were present in 12 cases and thymus-related syndromes were reported in 4. Histological subtypes were 1 AB, 2 B1, 4 B2, 7 B3, 1 mixed B1–B2, 1 mixed B1–B3 and 2 mixed B2–B3 thymomas. Neoadjuvant chemotherapy (4 courses of cisplatin-based chemotherapy) was well tolerated in all cases. Those patients demonstrating clinical response at restaging (16/18) received surgical resection: “en-bloc” thymoma, residual thymic tissue and tumour involved organs resection was carried out together with the pleural implants removal. Complete macroscopic resection was achieved 10/16 patients (64%). Postoperative mortality and morbidity were null and 24%, respectively. Adjuvant radiation therapy consisted of 45–54Gy administered by a 6MV linear accelerator to the whole mediastinum and previous tumour bed. Mean follow-up was 82±33months (range 31–143); overall survival was 85% and 53% at 5- and 10-years. Disease-related survival of the entire cohort was 100% and 58% at 5- and 10-years, whereas freedom from relapse survival for patients submitted to complete resection was 58% and 42% at 5- and 10-years. Disease-related survival when complete and not complete resection were considered were 100% and 52% and 72% and 0% at 5- and 10-years respectively (p=0.048). Multimodal management based on induction chemotherapy, subsequent surgery and postoperative mediastinal radiation allows a good complete resection rate and it is demonstrated to be a safe and effective treatment to warrant a good long-term survival in stage IVA thymoma patients.

Mixed germ cell tumor metastatic to the skin: Case report and literature review

BackgroundTesticular cancer is the most common cancer for males aged 15~35 years old. The initial presentation is typically an asymptomatic enlarged testicle. The retroperitoneum is the most common metastatic area. Other metastatic sites include the lung, liver, brain, adrenal glands, gastrointestinal tract and spleen. Skin metastasis is a rare event and frequently associated with poor prognosis.Case presentationA 19-year old male was diagnosed testicular mixed germ cell tumor with initial presentation of cutaneous metastasis at scalp and upper abdomen. After radical orchiectomy and four courses of cisplatin-based chemotherapy, the scalp and upper abdominal lesions regressed completely. The size of lung metastases remained unchanged.ConclusionsFor advanced stage testicular cancer, cisplatin-based chemotherapy is still effective to achieve partial response.

Myths and Facts on Adjuvant Carboplatin for Stage I Seminoma

5-year survival of 100%. 3,5 This relapse rate is in the range of that observed after radiation, recurrences are mostly retroperitoneal, and effective salvage is almost invariably obtained with four courses of cisplatin-based chemotherapy. Furthermore, an adequate follow-up (median, 72 months) in this pooled analysis precludes the chance of significant late adverse effects or late relapses, while showing a significant reduction in the probability of second germ-cell tumors. In this context, it is conceptually difficult to continue recommending systematic (indiscriminate) prophylactic radiation because more than 80% of these patients are cured with orchiectomy alone and the late hazards of radiotherapy (mainly second malignancies)arewellknown.Moreover,althoughpredictivefactorsfor

Adjuvant systemic chemotherapy in the treatment of patients with invasive transitional cell carcinoma of the upper urinary tract

Objectives To evaluate the efficacy of adjuvant systemic chemotherapy in conjunction with surgery in patients with invasive transitional cell carcinoma of the upper urinary tract. Methods From January 1991 to May 2001, 36 men and 7 women had invasive (Stage pT2 or worse), but not metastatic, disease and were the subjects of this study. Their median age was 59 years (range 36 to 72). Of these 43 patients, 32 were scheduled to receive more than four courses of cisplatin-based chemotherapy. The median follow-up period of all the evaluated patients was 30.7 months (range 4.7 to 98.8). Results Recurrence was observed in 12 patients (37.5%) who underwent chemotherapy and 7 (63.6%) who did not ( P = 0.170). The disease-free survival was lower in the nonchemotherapy group than in the chemotherapy group ( P = 0.0439). During the follow-up period, 9 patients (28.1%) in the chemotherapy group died and 9 patients (81.8%) in the nonchemotherapy group died ( P = 0.004). Multivariate Cox proportional hazard model analysis revealed that the use of adjuvant chemotherapy ( P = 0.006, relative risk = 9.19) and node-positive status ( P = 0.008, relative risk = 8.28) were strongly associated with overall survival. In the chemotherapy group, 24 (75%) had side effects due to the treatment; however, fever and gastrointestinal symptoms were the chief adverse effects and were well tolerated. Conclusions Our results have indicated that adjuvant systemic chemotherapy may provide therapeutic benefit in patients with invasive transitional cell carcinoma of the upper urinary tract.

A Randomised Crossover Study Comparing Ramosetron plus Dexamethasone with Ramosetron Alone in the Prevention of Cisplatin-Induced Emesis

To assess the efficacy and tolerability of a combination of ramosetron and dexamethasone compared with ramosetron alone in the prevention of cisplatin-induced emesis. Prospective, randomised, single-blind, crossover study. Thirty-four chemotherapy-naive patients with stomach cancer or sar-coma scheduled to receive two consecutive courses of cisplatin-based chemo-therapy. Patients were randomised to receive ramosetron (0.3mg intravenously [IV] on day 1 then 0.1mg orally [PO] once daily on days 2-6) either with or without dexamethasone (20mg IV on days 1-6). Those who completed the first chemotherapy cycle returned for a second cycle after 4 weeks and were crossed over to the alternate antiemetic treatment. In the first 24 hours, complete response was achieved in 84.8% of patients receiving ramosetron plus dexamethasone and in 59.4% of patients receiving ramosetron alone (p = 0.014). Furthermore, the combination ramosetron plus dexamethasone was significantly more effective in terms of time to first episode of vomiting and patient's preference. On day 2, patients who received ramosetron plus dexamethasone had a higher complete response rate than those who received ramosetron alone (p = 0.047). Adverse events were mild with no significant differences between the two groups. The combination of ramosetron plus dexamethasone was superior to ramosetron alone in preventing cisplatin-induced acute emesis. It is highly recommended that a combination of ramosetron plus dexamethasone rather than ramosetrone alone be given to patients receiving cisplatin-containing chemo-therapy.

Cisplatin-induced hypokalemic paralysis

IntroductionProfound hypokalemic conditions resulting from cisplatin therapy have been known to produce hypokalemic paralysis in rare cases. We describe such a case of cisplatin-induced hypokalemic paralysis. Case summaryA 15-year-old Persian girl with ovarian dysgerminoma presented with severe generalized weakness and paraplegia 1 week after the fourth course of cisplatin-based chemotherapy. On physical examination, there was symmetric flaccid paralysis and areflexia in all of the extremities and particularly in the lower limbs. Her serum potassium concentration was 1.7 mmol/L. Metastatic disease was excluded by a comprehensive systemic evaluation. Complete clinical and paraclinical recovery was achieved after short-term administration of potassium supplement. DiscussionAdverse drug reactions are common with cisplatin, but the drug is only rarely associated with hypokalemic paralysis. Based on the Naranjo causality algorithm, an objective assessment revealed cisplatin to be a probable cause of hypokalemic paralysis in this case. This adverse drug event—whether isolated or secondary to hypomagnesemia—may be deceptive, leading to a fatal mistake in the oncology setting, and should therefore be precisely differentiated from cancer-related complications. ConclusionsThis case suggests that cisplatin should be added to the list of agents causing hypokalemic paralysis. Regular serum electrolyte measurement, the early detection of cation deficiency, and appropriate replacement of cations are all recommended.

High-dose chemotherapy and hematopoietic stem cell transplantation for patients with nasopharyngeal cancer: a feasibility study.

Nasopharyngeal cancer (NPC) is a highly chemosensitive malignancy. The purpose of this study was to evaluate the clinical efficacy of high-dose chemotherapy (HDCT) in combination with hematopoietic stem cell transplantation in patients with locally advanced or metastatic NPC. Nine patients with locally advanced or metastatic NPC were recruited after three to four courses of cisplatin-based chemotherapy followed by a single course of cyclophosphamide 1600 mg/m(2) day 1-4, carboplatin 400 mg/m(2) day 1-3, and thiotepa 120 mg/m(2) day 1-4 or melphalan 120 mg/m(2) day 5. Chemoirradiation was administered after HDCT only if the patient had never received radiotherapy or had residual cervical nodes. A median of 8.32 x 10(6) CD34+ cells/kg was collected. Two patients were rendered disease-free before HDCT, one by massectomy and one by cisplatin-based chemotherapy. All patients recovered rapidly after peripheral blood stem cell transplantation (PBSCT). Among seven assessable patients, response to HDCT was observed in four patients. Only one patient achieved complete response after HDCT. The median time to failure and median survival after HDCT was eight and 18 months, respectively. One patient died of pulmonary hemorrhage two months after transplantation. No long-term disease-free survival was noted. HDCT with autologous PBSCT is feasible with an acceptable toxicity, and can convert partial remission into complete remission. While no long-term disease-free survival was observed in this study, further investigations are needed to establish the role of HDCT in the treatment of NPC.

Locally recurrent nasopharyngeal carcinoma

Purpose: To assess the outcome of and determine prognostic factors for locally recurrent nasopharyngeal carcinoma (NPC) in patients treated with a second course of radiotherapy (RT). Materials and methods: From 1982 to 1995, 186 NPC patients, who had initially been treated in the Department of Radiation Oncology, Chang Gung Memorial Hospital-Linkou, developed local recurrence in the nasopharynx and were re-treated with RT (≥20 Gy). The time from the initial RT to re-treatment ranged from 8 to 136 months (median: 23 months). All patients were treated with external RT and conformal radiotherapy was used in 35 patients after 1993. Fifteen received radiosurgery as a boost treatment. The RT dose at the nasopharyngeal tumor area ranged from 20 to 67.2 Gy (median 50 Gy). Eighty-two patients received one to eight courses of cisplatin-based chemotherapy in addition to RT. Results: The 1-, 3- and 5-year survival was 54.9, 22.1 and 12.4%, respectively. Patients whose tumor relapsed later than 2 years after the first treatment had a better survival than those with earlier relapse (3-year survival: 30.1 vs. 10.8%; P=0.015), but the difference became insignificant in patients who received ≥50 Gy. Patients without evidence of intracranial invasion or cranial nerve palsy had better survival than those with such lesions (3-year survival: 30.9 vs. 3.7%; P=0.006). A re-treatment dose ≥50 Gy yielded better survival (3-year survival: 22.8 vs. 18.5%; P=0.003). Addition use of radiosurgery may improve survival. The use of chemotherapy did not improve survival. Conformal radiotherapy resulted in significantly fewer severe complications than conventional RT. Conclusions: A repeat course of RT for locally recurrent NPC successfully prolongs survival in a significant number of patients. Intracranial invasion and/or cranial nerve palsy and re-treatment dose affect the prognosis, with a dose of ≥50 Gy significantly improving survival. Radiosurgery boost may also improve survival. Our preliminary data indicates that conformal radiotherapy may decrease the severity of radiation-induced complications. However; longer follow-up and larger sample size is necessary to document the findings.

Recent management of malignant ovarian germ cell tumors: a study of 34 cases.

To review the outcome of the treatment in patients with malignant ovarian Germ cell tumors with respect to survival and surgical management at a single institution during 1990-1996. Thirty-four patients with malignant ovarian Germ cell tumors were studied retrospectively for their surgical management. Fourteen patients had pure dysgerminoma, 11 endodermal sinus tumor, 6 immature teratoma, and 3 mixed Germ cell tumors. Nine patients had stage IA, 8 stage IC, 2 stage IIC, 8 stage III, 3 stage IV, and 4 referred patients with recurrent diseases. Nineteen patients underwent primary conservative surgery, 11 had primary nonconservative surgery. Twenty-two patients were treated with chemotherapy (BEP or EP or PVB regimen). Five patients with pure dysgerminoma received adjuvant radiotherapy. Persistent remission was achieved in 26 patients. Two patients (7.4%) had recurrence after remission. Seven patients had died of the diseases. Patients with complete clinical remission did not undergo second-look surgery. The overall survival was 78.8%, 100% for immature teratoma, 84.6% for pure dysgerminoma, 72.8% for endodermal sinus tumor, and 33.3% for mixed Germ cell tumors, with median follow-up time 31 (3-93) months. Patients with limited diseases regardless of histologic types can be safely managed by unilateral salpingo-oophorectomy followed by, if indicated, 3-4 courses of cisplatin-based chemotherapy. For advanced diseases, conservative surgery is advisable in patients with endodermal sinus tumor.

Primary mediastinal seminoma. Efficacy of chemo-radiotherapy alone.

A treatment policy must be established for primary mediastinal seminoma. We have treated five patients with this entity during 18 years. All our patients presented with a bulky mass as is usual for this disease. Our first patient was treated surgically and then with radiation, but developed recurrences and died 11 years after the initial diagnosis. Three subsequent patients, one with multiple lymph node metastases, were treated with radiation followed by cisplatin. Our most recent patient received two courses of adriamycin-reinforced PVB, and then radiation for consolidation, followed by another course of chemotherapy. For these five patients, the 5- and 10-year survival rates were both 100%. A review of the literature emphasized the fact that either radiation or surgery has recently been replaced by chemotherapy as the front-line treatment of this rare tumor in light of a better response to the latter form of treatment. We fully agree with this policy. Based on the favorable long-term results of our patients we conclude that chemo-radiotherapy can cure primary mediastinal seminoma, even in its extended form, without surgery. An initial three courses of cisplatin-based chemotherapy like adriamycin-reinforced PVB or BEP should be followed by radiation of up to 4,000 cGy for consolidation. Surgery may play a limited role for tumors that are small at presentation, or for any possible viable residue seen on roentgenograms following chemo-radiotherapy.

Accelerated Hyperfractionated Radiotherapy Combined with Induction and Concomitant Chemotherapy for Inoperable Non-small-cell Lung Cancer: Impact of Total Treatment Time

Tumour cell proliferation during conventionally fractionated radiotherapy (RT) can negatively influence the treatment outcome in patients with unresectable non-small-cell lung cancer (NSCLC). Accelerated and hyperfractionated RT may therefore have an advantage over conventional RT. Moreover, earlier studies have suggested improved survival with addition of cisplatin-based chemotherapy (CT). We present here the results of combined treatment with induction and concomitant CT and accelerated hyperfractionated RT in a retrospective series of patients with advanced NSCLC. Between August 1990 and August 1995, 90 consecutive patients, aged 42-77 years (median 63 years), with locally advanced unresectable or medically inoperable NSCLC and good performance status were referred for treatment: stage: I 23%, IIIa 37%, IIIb 40%. Patient histologies included: squamous cell carcinoma 52%, adenocarcinoma 34% and large cell carcinoma 13%. The treatment consisted of two courses of CT (cisplatin 100 mg/m2 day 1 and etoposide 100 mg/m2 day 1-3 i.v.), the second course given concomitantly with RT. The total RT dose was 61.2-64.6 Gy, with two daily fractions of 1.7 Gy. A one-week interval was introduced after 40.8 Gy to reduce acute toxicity, making the total treatment time 4.5 weeks. Concerning toxicity, 33 patients had febrile neutropenia, 10 patients suffered from grade III oesophagitis and 7 patients had grade III pneumonitis. There were two possible treatment-related deaths, one due to myocardial infarction and the other due to a pneumocystis carinii infection. The 1-, 2- and 3-year overall survival rates were 72%, 46% and 34%, respectively; median survival was 21.3 months. Fifty-nine patients had progressive disease: 21 failed locoregionally, 29 had distant metastases and 9 patients had a combination of these. Pretreatment weight loss was the only prognostic factor found, except for stage. However, the results for stage IIIb were no different from those for stage IIIa. We conclude that the survival results compare favourably with those of most other studies with a manageable toxicity.

Expression of glutathione S-transferase pi and cisplatin resistance in human ovarian cancer

Glutathione S-transferase π (GSTπ) expression in tumor cells is thought to relate to cisplatin resistance. We attempted to clarify immunohistochemically the correlation between GSTπ expression and clinical response in ovarian cancer. Fifty-nine patients with ovarian cancer underwent initial debulking surgery and received from three to five courses of cisplatin-based chemotherapy after surgery. Immunostaining for GSTπ was performed on formalin fixed sections of the patients’ tumor by the streptoavidin-biotin-peroxidase complex method. Positive staining of GSTπ was observed diffusely in nuclei and cytoplasm of cancer cells. Of 59 tumors, 38 (64.4%) were GSTπ positive. Twenty-three of 25 patients (92.0%) who showed no response to chemotherapy had GSTπ positive tumor cells. The predictive value of positive GSTπ staining for drug resistance was 79.3% (23/29). The 5-year survival rate of patients with GSTπ positive tumors was significantly lower than that of those with GSTπ negative tumors by the Kaplan-Meier method (P < 0.01). The results suggest that overexpression of GSTπ is related to resistance to cisplatin and to prognosis in patients with ovarian cancer.

Decline of posttreatment tumor marker levels after therapy of nonsmall cell lung cancer. A useful outcome predictor.

The assessment of treatment efficacy in nonsmall cell lung cancer (NSCLC) is limited by the lack of a clear association between clinical response and survival. The prognostic usefulness of treatment-induced tumor-marker declines in NSCLC has not been established. The authors investigated the prognostic significance of treatment-induced declination in tumor marker levels of carcinoembryonic antigen, CA 19-9, and CA 125 in a group of patients with NSCLC treated with a brief course of cisplatin-based chemotherapy. Eighty-three patients with NSCLC enrolled on 2 related treatment protocols had pretreatment tumor-marker determinations. Patients were restaged 10 to 12 weeks after study entry, and clinical and marker responses were determined. Thirty-eight patients (46%) had elevated pretreatment tumor markers, 36 (42%) of whom were evaluable for both clinical and marker responses. Pretreatment, the latter 36 individuals had measurable or evaluable disease, and at least one elevated tumor marker (greater than twice normal); posttreatment, they had follow-up measurements of both parameters. Of the 36 patients, 8 had normalization of tumor marker levels, 13 had 50-99% marker level declination, and 15 had less than 50% or no declination. In the same group of 36 patients, there were, 1 patient with complete clinical response, 11 with partial response, 19 with stable disease, and 5 with progressive disease. Marker responses occurred with equal frequency in clinical responders and nonresponders. There was no association between clinical response and survival, but there was a strong association between marker response and survival. In patients with nonsmall cell lung cancer with elevated pretreatment tumor marker levels, treatment-induced marker level declination can be a surrogate indicator for survival.

Prognostic significance of peritumoural blood and lymphatic vessel invasion by tumour cells in T4 non-small cell lung cancer following induction therapy

We investigated the impact of new biological prognostic factors is in 28 patients receiving a median of two courses of cisplatin-based chemotherapy with (n = 14) or without (n = 14) radiation and operation for stage IIIB (T4) non-small cell lung cancer (NSCLC). After induction therapy, 5 patients had a complete and 21 a partial response; 2 had a stable disease. A complete resection was made in 26 patients (93%). Five patients (18%) had their primary tumour and involved vestiges completely sterilized. In the remaining 23, the majority of the tumours showed abnormalities in the p53 gene expression (56%), harboured proliferating cells (91%) and induced angiogenesis (91%). Peritumoural blood and lymphatic vessel invasion (PBLVI) by tumour emboli was observed in 6 tumours. With a median follow-up of 25 months, overall 3-year survival was 48%; disease-free survival (DFS) has not been reached yet. The only significant factor influencing DFS in multivariate analysis was PBLVI by tumour cells; PBLVI-positive patients had a significantly higher likelihood ratio (P = 0.000001) of developing metastasis than their PBLVI-negative counterparts. This study documents the prognostic implication of PBLVI by tumour cells in T4 NSCLC.