A prospective randomized trial comparing high-dose cisplatin with low-dose cisplatin and chlorambucil in advanced ovarian carcinoma.

Sixty-one patients with FIGO stage III ovarian carcinoma and 30 patients with stage IV ovarian carcinoma were randomized to receive either high-dose cisplatin (100 mg/m2) or low-dose cisplatin (20 mg/m2) and chlorambucil. Overall response rates were similar in both arms, with 68% and 49% of stage III patients and 61% and 72% of stage IV patients responding to high-dose cisplatin and the combination, respectively. There was a strong trend for better survival in stage III (P less than .05) but not in stage IV patients treated with cisplatin alone. The toxicity suffered by patients treated with high-dose cisplatin was severe, and in 15 patients cisplatin therapy was stopped because of unacceptable toxicity.

Download Full-text

P2.17-10 Daily Low–Dose Cisplatin and High Dose Radiotherapy for Elderly Patients with Stage III NSCLC is Well Tolerated.

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2018.08.1536 ◽

2018 ◽

Vol 13 (10) ◽

pp. S855-S856

Author(s):

E.m.t. Dieleman ◽

R. Van Os ◽

W. Kolff ◽

C.c.e. Koning ◽

J.t. Annema ◽

...

Keyword(s):

Elderly Patients ◽

Low Dose ◽

Stage Iii ◽

High Dose ◽

Stage Iii Nsclc

Download Full-text

Crossover and rechallenge with pembrolizumab in recurrent patients from the EORTC 1325-MG/Keynote-054 phase 3 trial, pembrolizumab versus placebo after complete resection of high-risk stage III melanoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.9500 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 9500-9500

Author(s):

Alexander M. Eggermont ◽

Andrey Meshcheryakov ◽

Victoria Atkinson ◽

Christian U. Blank ◽

Mario Mandalà ◽

...

Keyword(s):

Disease Progression ◽

Objective Response ◽

Stage Iv ◽

Median Number ◽

Complete Resection ◽

Stage Iii ◽

Phase 3 ◽

Double Blind ◽

Grade 3 ◽

To Receive

9500 Background: The phase 3 double-blind EORTC 1325/KEYNOTE-054 trial evaluated pembrolizumab (pembro) vs placebo in stage III cutaneous melanoma patients (pts) with complete resection of lymph nodes. Pembro improved RFS (hazard ratio [HR] 0.57) and DMFS (HR 0.60) (Eggermont, NEJM 2018, TLO 2021). In the pembro group, the incidence of immune related AE (irAE) grade 1-5 was 37%, and of grade 3-5 was 7%. We present the safety profile, response rate and PFS for the subset of pts who had a recurrence and crossed over or were rechallenged with pembrolizumab, within protocol. Methods: Pts were randomized to receive iv. pembro 200 mg (N=514) or placebo (N=505) every 3 weeks for a total of 18 doses (~1 year). Upon recurrence with no brain metastases, pts with an ECOG PS 0-2 were eligible to enter part 2 of the study, i.e. to receive pembro 200 mg iv. every 3 weeks for a maximum of 2 years, for crossover (those who received placebo) or rechallenge (those who recurred ≥6 months after completing one year of pembro therapy). Treatment was stopped in case of disease progression (RECIST 1.1) or unacceptable toxicity. Results: At the clinical cut-off (16-Oct-2020), 298 (59%) pts had a disease recurrence in the placebo group; 155 pts participated in the crossover part 2 of the trial. A total of 297 (58%) pts completed the 1-yr pembro adjuvant treatment, of whom 47 had a recurrence ≥6 mths from the stop of treatment and 20 entered in the rechallenge part of the trial. Among 175 pts who started pembro in Part 2, 160 discontinued due to completion of therapy (N=24), disease progression (N=88), toxicity (N=20), investigator's decision (N=21), or other reason (N=7); 15 pts were still on-treatment. Results for the 2 groups are provided in the table. The median number of doses was 12 and 5.5, respectively (resp), and the median follow-up was 41 and 19 mts, resp. Among the 175 pts, 51 (29%) had a grade 1-4 irAE (by group: 47 [30%] and 4 [20%] resp) and 11 (6%) a grade 3-4 irAE. Conclusions: Pembrolizumab treatment after crossover yielded a 39% ORR in evaluable pts and an overall 3-yr PFS of ̃32%, but after rechallenge the efficacy was lower. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA The median PFS (95% CI) from start of Part 2 was 14 (5-27) and 8 (5-15) mts for stage III-resected and III/IV various, resp. Among the 80 stage IV crossover pts with evaluable disease, 31 (39%) had an objective response: 14 (18%) CR, 17 (21%) PR. The 2-yr PFS rate from response was 69% (95% CI 48-83%). For these 80 pts, the median PFS was 6.1 mts and the 3-yr PFS rate was 31% (95% CI 21-41%). Among 9 stage IV rechallenged pts with an evaluable disease, 1 (11%) reached CR, 3 had SD and 5 PD. Clinical trial information: NCT02362594. [Table: see text]

Download Full-text

Factors associated with palliative care (PC) utilization in advanced and metastatic renal cell carcinoma (RCC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.6_suppl.297 ◽

2021 ◽

Vol 39 (6_suppl) ◽

pp. 297-297

Author(s):

Hiren V. Patel ◽

Joshua Sterling ◽

Arnav Srivastava ◽

Sinae Kim ◽

Biren Saraiya ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Palliative Care ◽

Cell Carcinoma ◽

Renal Cell ◽

Multivariable Analysis ◽

Stage Iv ◽

Stage Iii ◽

Clinical Factors ◽

Factors Associated ◽

To Receive

297 Background: Palliative care (PC) offers various benefits for patient with cancer that include, but are not limited to, decrease in disease-specific symptoms and improvement in functional status. Several oncological guidelines have adopted early integration of PC into oncologic care to improve quality of life among patients with advanced malignancies. However, PC utilization patterns and factors associated with its use in advanced renal cell carcinoma (RCC) remain poorly understood. Methods: Using the National Cancer Database (NCDB), we abstracted patients with stage III and IV RCC from 2004-2014 and evaluated PC utilization amongst this cohort. Socioeconomic and clinical factors were compared for patient receiving and not receiving PC for advanced RCC. Multivariable logistic regression identified factors that were associated with receipt of PC. Results: We identified 20,122 and 42,014 patients with stage III and IV RCC, respectively. Among this cohort, 329 and 9,317 patients received PC for stage III and IV RCC, respectively. From 2004 to 2014, PC utilization has been stable at ~1% for stage III RCC and has significantly increased from 17% to 20% for stage IV RCC. Multivariable analysis demonstrated that Blacks, income >$48,000, regions outside of Northeast, stage III RCC, and patients that received surgery were less likely to receive PC. Patients that were female, with more comorbidities, uninsured or with government insurance, lower educational status, treated at academic or integrated cancer program, with sarcomatoid histology, receiving systemic therapy were more likely to receive PC. Conclusions: While PC utilization has significantly increased for stage IV RCC, there are several demographic, socioeconomic, and clinical factors that predict PC usage among patients with advanced RCC. Taken together, this suggests the need for more equitable and systematic use of PC among patients with advanced RCC.

Download Full-text

Carboplatin, doxorubicin, and cyclophosphamide versus cisplatin, doxorubicin, and cyclophosphamide: a randomized trial in stage III-IV epithelial ovarian carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.1991.9.4.658 ◽

1991 ◽

Vol 9 (4) ◽

pp. 658-663 ◽

Cited By ~ 43

Author(s):

P F Conte ◽

M Bruzzone ◽

F Carnino ◽

S Chiara ◽

M Donadio ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Randomized Trial ◽

Dosage Reduction ◽

Response Rate ◽

Residual Disease ◽

Epithelial Ovarian Carcinoma ◽

Stage Iii ◽

Similar Response ◽

Forced Diuresis ◽

To Receive

One hundred sixty-four patients with stage III-IV epithelial ovarian carcinoma were randomized to receive cisplatin (CDDP) 50 mg/mq, doxorubicin 45 mg/mq, and cyclophosphamide 600 mg/mq (PAC) or carboplatin 200 mg/mq, doxorubicin 45 mg/m2, and cyclophosphamide 600 mg/mq (CAC). To administer equitoxic doses at each cycle, the drug dosages were adjusted according to the hematologic toxicities experienced after the previous course; 44.7% of CAC and 21.1% of PAC patients required a dosage reduction at the second course (P = .002). Neither CAC nor PAC caused any clinically relevant neuro-nephrotoxicity; however, CDDP was administered with hydration and forced diuresis, while carboplatin was administered by rapid intravenous (IV) infusion. After six cycles, response rates were superimposable: 62.5% and 66.6% for CAC and PAC, respectively; pathologic complete responses (pCRs) were 16.7% for CAC and 23.2% for PAC; among patients with more than 2 cm residual disease, PAC induced more pCRs than CAC (eight of 52 or 15.4% v one of 42 or 2.4%, P = .07). Median survivals and progression-free survivals (PFSs) were 22.6 and 13.2 months for PAC, and 23.1 and 15.5 months for CAC, respectively; these differences are not significant. In conclusion, this trial demonstrates that equitoxic doses of PAC or CAC result in a similar response rate, PFS, and survival.

Download Full-text

Randomized trial comparing two combination chemotherapy regimens (CHAP-5 v CP) in advanced ovarian carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.8.1157 ◽

1987 ◽

Vol 5 (8) ◽

pp. 1157-1168 ◽

Cited By ~ 190

Author(s):

J P Neijt ◽

W W ten Bokkel Huinink ◽

M E van der Burg ◽

A T van Oosterom ◽

P H Willemse ◽

...

Keyword(s):

Ovarian Carcinoma ◽

Stage Iv ◽

Progression Free Survival ◽

Therapeutic Index ◽

Residual Tumor ◽

Figo Stage ◽

Gynecology And Obstetrics ◽

Adequate Hydration ◽

Karnofsky Index

One hundred ninety-one patients with advanced epithelial ovarian carcinoma were treated with either a combination of doxorubicin and a five-day course of cisplatin alternating with cyclophosphamide and hexamethylmelamine orally for 14 days (CHAP-5) or cyclophosphamide and cisplatin both administered intravenously (IV) on a single day at 3-week intervals (CP). At a median follow-up time of 45 months, treatment with each of these combinations resulted in the same remission rates (80% and 74%, respectively) and exactly the same progression-free survival and overall survival (median, 26 months). Despite adequate hydration, more renal toxicity was encountered in the CP-treated patients than in those who received CHAP-5. Disabling neurotoxicity and severe myelosuppression were encountered more frequently in the patients treated with CHAP-5. Because the toxicity was lower and CP treatment required shorter hospitalization, the single-day regimen was considered preferable for future use. The Karnofsky index was the only independent predictor for response, whereas both this index and the size of residual tumor before chemotherapy were predictive of survival. After correcting for other prognostic factors, it was determined that tumor size associated with improved survival was less than 1 cm. The site of metastases in International Federation of Gynecology and Obstetrics (FIGO) stage IV patients did not influence survival within this category. The results of this study confirm our previous findings that patients with microscopic remnants at second-look have a survival similar to that of patients who are histopathologically free of disease. This makes the significance of so-called pathologically confirmed complete remission questionable. The survival benefit of debulking surgery performed during chemotherapy seems only minimal for patients in whom debulking has already been attempted before treatment. Like others, we have found the CP regimen to have a good therapeutic index.

Download Full-text

Retinal toxicity after high-dose cisplatin therapy.

Journal of Clinical Oncology ◽

10.1200/jco.1985.3.12.1683 ◽

1985 ◽

Vol 3 (12) ◽

pp. 1683-1689 ◽

Cited By ~ 74

Author(s):

G Wilding ◽

R Caruso ◽

T S Lawrence ◽

Y Ostchega ◽

E J Ballintine ◽

...

Keyword(s):

Visual Acuity ◽

Ovarian Carcinoma ◽

Causal Relationship ◽

Color Vision ◽

Retinal Toxicity ◽

High Dose ◽

Visual Dysfunction ◽

Blurred Vision ◽

Cone Dysfunction ◽

Cisplatin Therapy

Because of increasing complaints of visual dysfunction, 13 patients with refractory or recently diagnosed ovarian carcinoma were evaluated for possible cisplatin-induced ophthalmologic toxicity. All patients had received high-dose cisplatin (200 mg/m2 in five divided daily doses) over two to four cycles. Eight patients (62%) developed symptoms of blurred vision and three (23%) also developed altered color perception. Retinal toxicity in the form of cone dysfunction was documented by electroretinography and color vision testing in 11 patients. Three patients were studied prospectively. Two patients who developed cone dysfunction had normal ophthalmologic exams before the initiation of chemotherapy or after one cycle of cisplatin, suggesting a causal relationship between cisplatin therapy and subsequent retinal abnormalities. Though visual acuity improved off therapy, color vision abnormalities persisted as long as 16 months beyond therapy.

Download Full-text

Successful treatment with minimal chemotherapy followed by low-dose involved field radiotherapy in children with Hodgkin's disease: A 20-year experience in a single institution in Greece

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.10052 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 10052-10052

Author(s):

A. G. Pourtsidis ◽

D. Doganis ◽

M. Baka ◽

D. Bouhoutsou ◽

M. Varvoutsi ◽

...

Keyword(s):

Complete Remission ◽

Hodgkin's Disease ◽

Low Dose ◽

Early Stage ◽

Hodgkin’S Disease ◽

Combined Modality Therapy ◽

Stage Iv ◽

High Dose ◽

Main Question ◽

Radio Therapy

10052 Background: The vast majority of children with Hodgkin's disease (HD) nowadays have an excellent chance of definite cure. The high curative rates as well as the prevention of late effects have to be among aims when managing children with HD. The purpose of our retrospective study was to report the outcome and prognostic factors of patients (pts) less than 15 years of age with HD treated with chemotherapy (CT) followed by low dose radiation from 1987 to 2006. Methods: We studied 58 children analyzing the following data: age, sex, stage, histology, therapy correlating these with the outcome of pts. Among 35 boys and 23 girls, age at diagnosis 4.5 - 15 years (median 12), all aged 7 years or less were boys (8/58). Nodurar sclerosis was the predominant histology subtype (69%) and 45% had advanced disease (stages III or IV). According the study period pts with early stage received 4 cycles of ABVD or VBVP and those with advanced stage disease alternating 3 cycles of MOPP/ABVD or 2 of MOPP/ABVP for stage III and alternating 3 cycles of MOPP/ABVD or 2 OPPA plus 4 COPP for stage IV. All pts had a good response (more than a 70% reduction) after initial CT and received 20 Gy of RT to initially involved fields. Results: Complete remission (CR) was achieved in all patients. Chemo- and radio-therapy were well tolerated. Fifty-three pts (DFS: 91.4%) live in their first complete remission. In 5 pts (8.6 %) relapse occurred, 20 -65 months from dx (median 25 mo). All received salvage treatment in combination with high dose CT and autologous stem-cell transplantation (SCT). Of the 5 relapsed all live 21 - 207 months (median 75 mo) from the dx of relapse and 41 - 232 mo (median 99) from the dx of disease. Second (thyroid cancer) plus third malignancy in one (osteosarcoma) was detected in 3 pts and all are alive. Finally for our group the overall survival is 100% and all children are alive 25 - 264 mo from dx (median 145 mo) and the event free survival is 86.2% (50/58). No factors related to the outcome were detected. Conclusions: In conclusion combined-modality therapy remains the standard of care for children with HD. However, there may be a significant number who can be cured with chemotherapy alone. At this moment the main question is: who can be cured without RT? No significant financial relationships to disclose.

Download Full-text

Phase III trial of high-dose interferon alpha-2b versus cisplatin, vinblastine, DTIC plus IL-2 and interferon in patients with high-risk melanoma (SWOG S0008): An intergroup study of CALGB, COG, ECOG, and SWOG.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.8504 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 8504-8504 ◽

Cited By ~ 9

Author(s):

Lawrence E. Flaherty ◽

James Moon ◽

Michael B. Atkins ◽

Ralph Tuthill ◽

John A. Thompson ◽

...

Keyword(s):

High Risk ◽

Stage Iv ◽

Phase Iii ◽

Stage Iii ◽

Rank Test ◽

High Dose ◽

Phase Iii Trial ◽

High Risk Melanoma ◽

Risk Melanoma ◽

High Dose Interferon

8504 Background: High-dose interferon for one year (HDI) is the FDA approved adjuvant therapy for patients (pts) with high-risk melanoma (HRM). Efforts to modify IFN dose or schedule have not improved efficacy. A meta-analysis demonstrated that biochemotherapy (BCT) produced superior response rates compared with chemotherapy in pts with stage IV melanoma (Wheatley et al J Clin Oncol 25:5426, 2007). We sought to determine whether a short course of BCT would be more effective than HDI as adjuvant treatment in pts with HRM. Methods: S-0008 (an Intergroup Phase III trial) enrolled pts who were high risk (Stage III A-N2a thru Stage III C N3) and randomized them to receive either HDI or BCT consisting of dacarbazine 800 mg/m2 day 1, cisplatin 20 mg/m2/ days 1-4, vinblastine 1.2 mg/m2 days 1-4, IL-2 9 MIU/m2/day continuous IV days 1-4, IFN 5 MU/m2/day sc days 1-4, 8,10,12, and G-CSF 5 ug/kg/day sc days 7-16. BCT cycles were given every 21 days x 3 cycles (9 weeks total). Pts were stratified for number of involved nodes (1-3 v ≥4), micro v macro metastasis, and ulceration of the primary. Co-primary endpoints were relapse free survival (RFS) and overall survival (OS) using a one-sided log rank test at p= 0.05. Results: 432 pts were enrolled between 8/2000 and 11/2007: 30 were ineligible or withdrew consent. Grade 3 and 4 adverse events occurred in 57% and 7% respectively of HDI pts and 36% and 40% of BCT pts. At a median f/up of 6 yrs, BCT improved RFS (p = 0.02, HR 0.77 [90% CI: 0.62 – 0.96]) with median RFS for BCT of 4.0 yrs (90% CI:1.9 – 5.9) v 1.9 yrs (90% CI: 1.4 – 2.5) and 5 yr RFS of 47% v 39%. Median OS was not different between the two arms (p = 0.49 HR 1.0 [90% CI: 0.78 – 1.27]) with median OS not yet reached for BCT v 8.4 yrs (90% CI: 4.5 – 9.3) for HDI and 5 yr survival 56% for both arms. Conclusions: In HRM pts, BCT provides a statistically significant improvement in RFS compared to HDI, but no discernable difference in OS and more grade IV toxicity. BCT represents a shorter, alternative treatment for pts with HRM, and a potential control arm and basis for future combinations in the adjuvant setting.

Download Full-text

Impact of Addition of Maintenance Therapy to Intensive Induction and Consolidation Chemotherapy for Childhood Acute Myeloblastic Leukemia: Results of a Prospective Randomized Trial, LAME 89/91

Journal of Clinical Oncology ◽

10.1200/jco.2002.07.300 ◽

2002 ◽

Vol 20 (12) ◽

pp. 2774-2782 ◽

Cited By ~ 52

Author(s):

Yves Perel ◽

Anne Auvrignon ◽

Thierry Leblanc ◽

Jean-Pierre Vannier ◽

Gerard Michel ◽

...

Keyword(s):

Overall Survival ◽

Maintenance Therapy ◽

Low Dose ◽

Disease Free Survival ◽

High Dose ◽

Induction Phase ◽

Consolidation Therapy ◽

Free Survival ◽

Childhood Acute Myeloid Leukemia ◽

To Receive

PURPOSE: To determine whether the use of maintenance therapy (MT) delivered after intensive induction and consolidation therapy confers any advantage in childhood acute myeloid leukemia (AML). PATIENTS AND METHODS: A total of 268 children with AML were registered in the Leucámie Aiquë Myéloïde Enfant (LAME) 89/91 protocol. This regimen included an intensive induction phase (mitoxantrone plus cytarabine) and, for patients without allograft, two consolidation courses, one containing timed-sequential high-dose cytarabine, asparaginase, and amsacrine. In the LAME 89 pilot study, patients were given an additional MT consisting of mercaptopurine and cytarabine for 18 months. In the LAME 91 trial, patients were randomized to receive or not receive MT. RESULTS: A total of 241 (90%) of 268 patients achieved a complete remission. The overall survival and event-free survival at 6 years were 60% ± 6% and 48% ± 6%, respectively. For the complete responders after consolidation therapy, the 5-year disease-free survival was not significantly different in MT-negative and in MT-positive randomized patients (respectively, 60% ± 19% v 50% ± 15%; P = .25), whereas the 5-year overall survival was significantly better in MT-negative randomized patients (81% ± 13% v 58% ± 15%; P = .04) due to a higher salvage rate after relapse. CONCLUSION: More than 50% of patients can be cured of AML in childhood. Either drug intensity or each of the induction and postremission phases may have contributed to the outstanding improvement in outcome. Low-dose MT is not recommended. Exposure to this low-dose MT may contribute to clinical drug resistance and treatment failure in patients who experience relapse.

Download Full-text