Phase II study of irinotecan combined with cisplatin in patients with previously untreated small-cell lung cancer. West Japan Lung Cancer Group.

PURPOSE Irinotecan (CPT-11) is effective against small-cell lung cancer (SCLC) as monotherapy. Cisplatin is also a key drug against SCLC. We conducted a phase II study of CPT-11 combined with cisplatin to evaluate the efficacy and toxicity of this regimen in patients with previously untreated SCLC. PATIENTS AND METHODS Seventy-five patients with previously untreated SCLC were enrolled onto the study. CPT-11 60 mg/m2 was administered intravenously on days 1, 8, and 15 in combination with cisplatin 60 mg/m2 on day 1 every 28 days. Four courses of chemotherapy followed by thoracic irradiation were given to patients with limited disease (LD) and six courses to patients with extensive disease (ED). RESULTS The overall response rate was 84%, with a complete response (CR) rate of 29%. Forty patients with LD achieved an overall response rate of 83% and a CR rate of 30% and 35 patients with ED achieved an overall response rate of 86% and a CR rate of 29%. The median response duration was 8.0 months for LD patients and 6.6 months for ED patients. The median survival was 14.3 months for LD patients and 13.0 months for ED patients. The major grade 3 or 4 toxicities were neutropenia (77%), leukopenia (45%), diarrhea (19%), and anemia (39%). Two patients died with concomitant neutropenia and diarrhea. CONCLUSION This is a new active regimen for SCLC, especially ED-SCLC, with acceptable toxicity. A phase III study that compares CPT-11/cisplatin with etoposide/cisplatin for ED-SCLC is now being conducted.

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Immunotherapy in non-small cell lung cancer and the abscopal effect.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e18104 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e18104-e18104

Author(s):

Syed Imran Mustafa Jafri ◽

Faizan Malik ◽

Naveed Ali ◽

Mary Naglak ◽

Mark L. Sundermeyer

Keyword(s):

Lung Cancer ◽

Side Effects ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Stable Disease ◽

Overall Response Rate ◽

Response Rate ◽

Small Cell ◽

Small Cell Lung ◽

Overall Response

e18104 Background: Advanced research and better understanding of the human immune system has led to the development of targeted immunotherapy such as PD-1 inhibitors. We studied patients with both squamous and non-squamous Non-Small Cell Lung Cancer in a community setting who are being treated with Nivolumab. Our primary objective was to determine response to therapy (overall response rate-ORR). Our secondary objective was to study the abscopal response of our population and if the tumor response was better in those patients who received radiotherapy in the preceding 6 months of the start of immunotherapy Methods: Data were summarized using descriptive statistics including means, standard deviations, medians, frequencies and percentages. Chi square analyses were used to make comparisons between response and categorical variables. Overall response rate was calculated by combining people with partial and complete response. All p-values were two tailed and a level of ≤ 0.05 was considered significant. Results: Out of 21 patients, eight (38%) did not show any disease progression. Five out of these eight patients (23% of total study population) had stable disease. Three remaining patients had partial response to the treatment. The ORR was 14% which is comparable to 20% and 19% ORR in the CheckMate trials for nivolumab. Thirteen (62%) patients had progressive disease. Our study showed no significant effect of radiotherapy on disease response to nivolumab. There was one incidence of treatment discontinuation permanently due to the side effects of Nivolumab. Conclusions: Immunotherapy is a promising new option in lung cancer treatment. Fewer side effects and improved survival compared to traditional second line chemotherapy makes it more appealing. In our study group, nivolumab has shown ORR of 14% and stable disease in an additional 23% of the patients resulting in a disease control rate of 37%.

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Combination chemotherapy with carboplatin, etoposide, and vincristine as first-line treatment in small-cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.5.818 ◽

1992 ◽

Vol 10 (5) ◽

pp. 818-823 ◽

Cited By ~ 17

Author(s):

U Gatzemeier ◽

D K Hossfeld ◽

R Neuhauss ◽

M Reck ◽

W Achterrath ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Overall Response Rate ◽

Response Rate ◽

Small Cell ◽

Small Cell Lung ◽

Limited Disease ◽

Extensive Disease ◽

Overall Response

PURPOSE The antineoplastic activity of carboplatin and etoposide may be improved by the addition of vincristine (CEV) because of its low myelosuppressive potential and its activity in small-cell lung cancer (SCLC). A phase II study with CEV was carried out. PATIENTS AND METHODS One hundred twenty-one untreated patients with SCLC (63 with limited disease [LD], 58 with extensive disease [ED]) were treated with a combination of 300 mg/m2 intravenous (IV) on day 1, etoposide 140 mg/m2 IV daily on days 1 to 3, and vincristine 1.4 mg/m2 IV on days 1, 8, and 15 every 4 weeks. RESULTS A 90% rate overall response rate including 56% complete responses (CRs) was achieved in LD and an 83% overall response rate including 35% CRs was observed in ED. Median survival time was 13 months in limited disease and 9.5 months in extensive disease. The 24 and 36 months survival rates were 29% in LD and 9% in ED. Myelosuppression was the main form of toxicity. CONCLUSION The combination of CEV is a new active and well-tolerated regimen in the treatment of SCLC. Prospective randomized studies of CEV with conventional chemotherapy are warranted.

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VAC chemotherapy with valproic acid for refractory/relapsing small cell lung cancer: a phase II study

ERJ Open Research ◽

10.1183/23120541.00029-2015 ◽

2015 ◽

Vol 1 (2) ◽

pp. 00029-2015 ◽

Cited By ~ 2

Author(s):

Thierry Berghmans ◽

Jean-Jacques Lafitte ◽

Arnaud Scherpereel ◽

Lieveke Ameye ◽

Marianne Paesmans ◽

...

Keyword(s):

Lung Cancer ◽

Valproic Acid ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Cell Lung Cancer ◽

Response Rate ◽

Phase Ii Study ◽

Objective Response ◽

Small Cell ◽

Small Cell Lung

Salvage chemotherapy (CT) for relapsing or refractory small cell lung cancer (SCLC) remains disappointing. In vitro experiments showed that valproic acid increases apoptosis of SCLC cell lines exposed to doxorubicin, vindesine and bis(2-chloroethyl)amine. The primary objective of this phase II study was to determine whether epigenetic modulation with valproic acid in addition to a doxorubicin, vindesine and cyclophosphamide (VAC) regimen improves 6-month progression-free survival (PFS).Patients with pathologically proven SCLC refractory to prior platinum derivatives and etoposide were eligible. After central registration, patients received VAC plus daily oral valproic acid.64 patients were registered, of whom six were ineligible. Seven patients did not receive any CT, leaving 51 patients assessable for the primary end-point. The objective response rate was 19.6%. Median PFS was 2.8 months (95% CI 2.5–3.6 months) and 6-month PFS was 6%. Median survival time was 5.9 months (95% CI 4.7–7.5 months). Toxicity was mainly haematological, with 88% and 26% grade 3–4 neutropenia and thrombopenia, respectively.Despite an interesting response rate, the addition of valproic acid to VAC did not translate into adequate PFS in relapsing SCLC or SCLC refractory to platinum–etoposide.

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P2-210: Induction Therapy (IT) of non small cell lung cancer (NSCLC) with reliable response rate and low treatment related morbidity and mortality, a phase II study

Journal of Thoracic Oncology ◽

10.1097/01.jto.0000283918.72561.02 ◽

2007 ◽

Vol 2 (8) ◽

pp. S655

Author(s):

Kyu H. Shin ◽

Andrew Y. Soh ◽

Hiroshi Takita

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Phase Ii ◽

Induction Therapy ◽

Cell Lung Cancer ◽

Response Rate ◽

Phase Ii Study ◽

Small Cell ◽

Morbidity And Mortality ◽

Small Cell Lung

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A randomized trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.9.1333 ◽

1989 ◽

Vol 7 (9) ◽

pp. 1333-1340 ◽

Cited By ~ 288

Author(s):

M L Slevin ◽

P I Clark ◽

S P Joel ◽

S Malik ◽

R J Osborne ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Overall Response Rate ◽

Response Rate ◽

Single Agent ◽

Small Cell ◽

Cytotoxic Action ◽

Small Cell Lung ◽

Overall Response

Etoposide is an increasingly used and well-tolerated drug in cancer medicine. Its cytotoxic action is phase-specific and it has demonstrated schedule dependency in both in vitro and animal studies, but clinical evidence of the importance of drug scheduling is uncertain. The two administration schedules of etoposide that have been compared in this randomized study of 39 patients with previously untreated extensive small-cell lung cancer treated with single-agent etoposide were 500 mg/m2 as a continuous intravenous (IV) infusion over 24 hours or five consecutive daily 2-hour infusions each of 100 mg/m2. Both regimens were repeated every 3 weeks, for a maximum of six cycles. Patients received combination chemotherapy with vincristine, doxorubicin, and cyclophosphamide (VAC) or radiotherapy on failure to respond or at relapse, depending on their Karnofsky performance status. The same therapy was used in both arms of the study. All patients are evaluable for response to etoposide. In the 24-hour arm, two patients achieved a partial remission, resulting in an overall response rate of 10%. In the 5-day schedule, 16 patients had a partial response and one had a complete remission, producing an overall response rate of 89%, which was significantly superior to that in the 24-hour arm (P less than .001). The median duration of remission to etoposide in the 5-day arm was 4.5 months. Bone marrow toxicity was similar in both schedules. Etoposide pharmacokinetics were measured in all patients, and total areas under the concentration versus time curves (AUCs) were equivalent in both regimens. This study has clearly demonstrated the importance of etoposide scheduling in humans, and the superiority of five daily infusions over a 24-hour continuous infusion. The response rate to single-agent etoposide using an efficacious schedule in extensive small-cell lung cancer has been determined to be in excess of 80%.

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